7-100953392-C-G

Position:

• chr7-100953392-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005960.2(MUC3A):​c.1613C>G​(p.Ser538Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 4/5 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 81)
• Consequence: MUC3A NM_005960.2 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.372

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11466244).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC3A	NM_005960.2	c.1613C>G	p.Ser538Cys	missense_variant	2/12	ENST00000379458.9	NP_005951.1
LOC105375431	XR_007060457.1	n.44-6641G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC3A	ENST00000379458.9	c.1613C>G	p.Ser538Cys	missense_variant	2/12	5	NM_005960.2	ENSP00000368771.5
MUC3A	ENST00000483366.5	c.1613C>G	p.Ser538Cys	missense_variant	2/11	5		ENSP00000483541.1

Frequencies

GnomAD3 genomes Cov.: 81

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 81

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Lung cancer Pathogenic:1

Pathogenic, no assertion criteria provided

research

Arun Kumar Laboratory, Indian Institute of Science

Jun 15, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
CADD	Benign	14
LIST_S2	Benign	0.42	T;T
MetaRNN	Benign	0.11	T;T
Sift4G	Uncertain	0.038	D;D
Vest4		0.13
gMVP		0.034

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: -;