19-29699309-T-TA

Variant names:

• chr19-29699309-T-TA
• rs139713991
• NM_031448.6:c.*3402dupT

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BS1_Supporting

The NM_031448.6(C19orf12):​c.*3402dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00133 in 336,910 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000096 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0023 (0 hom.)
• Consequence: C19orf12 NM_031448.6 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.50

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00227 (434/191334) while in subpopulation MID AF= 0.00452 (3/664). AF 95% confidence interval is 0.00218. There are 0 homozygotes in gnomad4_exome. There are 247 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C19orf12	NM_031448.6	c.*3402dupT		3_prime_UTR_variant	Exon 3 of 3	ENST00000323670.14	NP_113636.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C19orf12	ENST00000323670	c.*3402dupT		3_prime_UTR_variant	Exon 3 of 3	2	NM_031448.6	ENSP00000313332.9

Frequencies

GnomAD3 genomes AF: 0.0000962 AC: 14 AN: 145498 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000764

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000206

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000199

Gnomad SAS AF: 0.000219

Gnomad FIN AF: 0.000108

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000755

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00227 AC: 434 AN: 191334 Hom.: 0 Cov.: 0 AF XY: 0.00224 AC XY: 247 AN XY: 110126

Gnomad4 AFR exome AF: 0.00247

Gnomad4 AMR exome AF: 0.00281

Gnomad4 ASJ exome AF: 0.00248

Gnomad4 EAS exome AF: 0.000581

Gnomad4 SAS exome AF: 0.00206

Gnomad4 FIN exome AF: 0.00187

Gnomad4 NFE exome AF: 0.00242

Gnomad4 OTH exome AF: 0.00205

GnomAD4 genome AF: 0.0000962 AC: 14 AN: 145576 Hom.: 0 Cov.: 31 AF XY: 0.000113 AC XY: 8 AN XY: 70742

Gnomad4 AFR AF: 0.0000762

Gnomad4 AMR AF: 0.000206

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000200

Gnomad4 SAS AF: 0.000219

Gnomad4 FIN AF: 0.000108

Gnomad4 NFE AF: 0.0000755

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Neurodegeneration with brain iron accumulation 4 Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs139713991; hg19: chr19-30190216;