Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS1
The NM_031448.6(C19orf12):c.216G>A(p.Pro72Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000144 in 1,614,196 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
C19orf12 (HGNC:25443): (chromosome 19 open reading frame 12) This gene encodes a small transmembrane protein. Mutations in this gene are a cause of neurodegeneration with brain iron accumulation-4 (NBIA4), but the specific function of the encoded protein is unknown. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]
Our verdict: Benign. The variant received -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 19-29702922-C-T is Benign according to our data. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-29702922-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-5.36 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0000788 (12/152314) while in subpopulation SAS AF = 0.000621 (3/4832). AF 95% confidence interval is 0.000215. There are 0 homozygotes in GnomAd4. There are 6 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
Neurodegeneration with brain iron accumulation 4Benign:1
Jan 12, 2018
Illumina Laboratory Services, Illumina
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -