rs753854746

chr3-195781795-G-GCAchr3-195781795-G-GCCchr3-195781795-G-GCCTGACCchr3-195781795-G-GCT

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1

The NM_018406.7(MUC4):c.9784_9785insTG(p.Thr3262MetfsTer998) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.000011 (0 hom., cov: 0)
  • Exomes 𝑓: 9.7e-7 (0 hom.)
  • Failed GnomAD Quality Control
• 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 Likely_pathogenic. Variant got 8 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC4	NM_018406.7	c.9784_9785insTG	p.Thr3262MetfsTer998	frameshift_variant	2/25	ENST00000463781.8
MUC4	NM_004532.6	c.83-3341_83-3340insTG		intron_variant
MUC4	NM_138297.5	c.83-7491_83-7490insTG		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC4	ENST00000463781.8	c.9784_9785insTG	p.Thr3262MetfsTer998	frameshift_variant	2/25	5	NM_018406.7	A2

Frequencies

GnomAD3 genomes AF: 0.0000115 AC: 1 AN: 87040 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000394

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.71e-7 AC: 1 AN: 1029472 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 499546

Gnomad4 AFR exome AF: 0.00

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: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000115 AC: 1 AN: 87116 Hom.: 0 Cov.: 0 AF XY: 0.0000237 AC XY: 1 AN XY: 42150

Gnomad4 AFR AF: 0.0000393

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: 0.00

Gnomad4 OTH AF: 0.00

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;