3-195781795-G-GCCTGACC

Position:

• chr3-195781795-G-GCCTGACC

Variant summary

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

The NM_018406.7(MUC4):​c.9784_9785insGGTCAGG​(p.Thr3262ArgfsTer18) 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: not found (cov: 0)
• Consequence: MUC4 NM_018406.7 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74

Genes affected

MUC4 (HGNC:7514): (mucin 4, cell surface associated) The major constituents of mucus, the viscous secretion that covers epithelial surfaces such as those in the trachea, colon, and cervix, are highly glycosylated proteins called mucins. These glycoproteins play important roles in the protection of the epithelial cells and have been implicated in epithelial renewal and differentiation. This gene encodes an integral membrane glycoprotein found on the cell surface, although secreted isoforms may exist. At least two dozen transcript variants of this gene have been found, although for many of them the full-length transcript has not been determined or they are found only in tumor tissues. This gene contains a region in the coding sequence which has a variable number (>100) of 48 nt tandem repeats. [provided by RefSeq, Jul 2008]

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
MUC4	NM_018406.7	c.9784_9785insGGTCAGG	p.Thr3262ArgfsTer18	frameshift_variant	2/25	ENST00000463781.8	NP_060876.5
MUC4	NM_004532.6	c.83-3341_83-3340insGGTCAGG		intron_variant			NP_004523.3
MUC4	NM_138297.5	c.83-7491_83-7490insGGTCAGG		intron_variant			NP_612154.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC4	ENST00000463781.8	c.9784_9785insGGTCAGG	p.Thr3262ArgfsTer18	frameshift_variant	2/25	5	NM_018406.7	ENSP00000417498	A2

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.00000725 AC: 1 AN: 137916 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 73290

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000435

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs753854746; hg19: chr3-195508666;