chr1-12847525-AT-A

Variant names:

• chr1-12847525-AT-A
• rs767679031
• NM_001013631.3:c.764delA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001013631.3(HNRNPCL1):​c.764delA​(p.Asp255ValfsTer15) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000535 in 149,472 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000054 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000054 (6 hom.)
  • Failed GnomAD Quality Control
• Consequence: HNRNPCL1 NM_001013631.3 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.94

Genes affected

HNRNPCL1 (HGNC:29295): (heterogeneous nuclear ribonucleoprotein C like 1) Enables identical protein binding activity. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNRNPCL1	NM_001013631.3	c.764delA	p.Asp255ValfsTer15	frameshift_variant	Exon 2 of 2	ENST00000317869.7	NP_001013653.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNRNPCL1	ENST00000317869.7	c.764delA	p.Asp255ValfsTer15	frameshift_variant	Exon 2 of 2	1	NM_001013631.3	ENSP00000365370.4

Frequencies

GnomAD3 genomes AF: 0.0000535 AC: 8 AN: 149472 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000492

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000889

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000160 AC: 4 AN: 250618 Hom.: 0 AF XY: 0.00000738 AC XY: 1 AN XY: 135522

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000535 AC: 78 AN: 1456642 Hom.: 6 Cov.: 34 AF XY: 0.0000428 AC XY: 31 AN XY: 724620

Gnomad4 AFR exome AF: 0.0000899

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000640

Gnomad4 OTH exome AF: 0.0000665

GnomAD4 genome AF: 0.0000535 AC: 8 AN: 149472 Hom.: 0 Cov.: 30 AF XY: 0.0000412 AC XY: 3 AN XY: 72794

Gnomad4 AFR AF: 0.0000492

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000889

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000567

EpiCase AF: 0.000164

EpiControl AF: 0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Mayer-Rokitansky-Kuster-Hauser syndrome Uncertain:1

Oct 12, 2016

Mayo Clinic Laboratories, Mayo Clinic

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)		0.0		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: rs767679031; hg19: chr1-12907378;