19-29699312-A-AT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_031448.6(C19orf12):c.*3399_*3400insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00448 in 369,324 control chromosomes in the GnomAD database, including 27 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0097 (24 hom., cov: 30)
  • Exomes 𝑓: 0.00081 (3 hom.)
• Consequence: C19orf12 NM_031448.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.628

Genes affected

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 19-29699312-A-AT is Benign according to our data. Variant chr19-29699312-A-AT is described in ClinVar as [Likely_benign]. Clinvar id is 328662.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00973 (1477/151864) while in subpopulation AFR AF= 0.0341 (1410/41368). AF 95% confidence interval is 0.0326. There are 24 homozygotes in gnomad4. There are 685 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 24 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C19orf12	NM_031448.6	c.*3399_*3400insA		3_prime_UTR_variant	3/3	ENST00000323670.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C19orf12	ENST00000323670.14	c.*3399_*3400insA		3_prime_UTR_variant	3/3	2	NM_031448.6	P1

Frequencies

GnomAD3 genomes AF: 0.00971 AC: 1474 AN: 151748 Hom.: 24 Cov.: 30

Gnomad AFR AF: 0.0341

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00289

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000417

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00672

GnomAD3 exomes AF: 0.00220 AC: 163 AN: 73934 Hom.: 3 AF XY: 0.00180 AC XY: 75 AN XY: 41704

Gnomad AFR exome AF: 0.0301

Gnomad AMR exome AF: 0.00111

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000638

Gnomad OTH exome AF: 0.000887

GnomAD4 exome AF: 0.000814 AC: 177 AN: 217460 Hom.: 3 Cov.: 0 AF XY: 0.000671 AC XY: 84 AN XY: 125136

Gnomad4 AFR exome AF: 0.0291

Gnomad4 AMR exome AF: 0.00109

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000699

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000322

Gnomad4 OTH exome AF: 0.000999

GnomAD4 genome AF: 0.00973 AC: 1477 AN: 151864 Hom.: 24 Cov.: 30 AF XY: 0.00923 AC XY: 685 AN XY: 74226

Gnomad4 AFR AF: 0.0341

Gnomad4 AMR AF: 0.00289

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00665

Alfa AF: 0.00969 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Neurodegeneration with brain iron accumulation 4 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs113192583; hg19: chr19-30190219;