chr7-100952650-AC-A

Position:

• chr7-100952650-AC-A

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_005960.2(MUC3A):​c.873delC​(p.Ile292fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.000082 (0 hom., cov: 43)
  • Failed GnomAD Quality Control
• Consequence: MUC3A NM_005960.2 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: -2.03

Genes affected

MUC3A (HGNC:7513): (mucin 3A, cell surface associated) The mucin genes encode epithelial glycoproteins, some of which are secreted and some membrane bound. Each of the genes contains at least one large domain of tandemly repeated sequence that encodes the peptide sequence rich in serine and/or threonine residues, which carries most of the O-linked glycosylation (Gendler and Spicer, 1995 [PubMed 7778880]).[supplied by OMIM, Aug 2008]

LOC105375431 (HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC3A	NM_005960.2	c.873delC	p.Ile292fs	frameshift_variant	2/12	ENST00000379458.9	NP_005951.1
LOC105375431	XR_007060457.1	n.44-5900delG		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC3A	ENST00000379458.9	c.873delC	p.Ile292fs	frameshift_variant	2/12	5	NM_005960.2	ENSP00000368771.5
MUC3A	ENST00000483366.5	c.873delC	p.Ile292fs	frameshift_variant	2/11	5		ENSP00000483541.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 12 AN: 145852 Hom.: 0 Cov.: 43 FAILED QC

Gnomad AFR AF: 0.0000758

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000691

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000199

Gnomad SAS AF: 0.000438

Gnomad FIN AF: 0.0000983

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000458

Gnomad OTH AF: 0.000502

GnomAD4 exome Cov.: 79

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000822 AC: 12 AN: 145956 Hom.: 0 Cov.: 43 AF XY: 0.000112 AC XY: 8 AN XY: 71274

Gnomad4 AFR AF: 0.0000756

Gnomad4 AMR AF: 0.0000690

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000199

Gnomad4 SAS AF: 0.000438

Gnomad4 FIN AF: 0.0000983

Gnomad4 NFE AF: 0.0000458

Gnomad4 OTH AF: 0.000497

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

Submissions by phenotype

Small cell lung carcinoma Pathogenic:1

Pathogenic, no assertion criteria provided

research

Arun Kumar Laboratory, Indian Institute of Science

Jun 15, 2021

- -

Lung cancer Pathogenic:1

Pathogenic, no assertion criteria provided

research

Arun Kumar Laboratory, Indian Institute of Science

Jun 15, 2021

- -

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: rs765973058; hg19: chr7-100550290;