chr3-195779087-CGGTGACAGGAAGAGAGGTGGTGTGACCTGAGGATGCTGAGGAAGGGAT-C

Position:

• chr3-195779087-CGGTGACAGGAAGAGAGGTGGTGTGACCTGAGGATGCTGAGGAAGGGAT-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM4

The NM_018406.7(MUC4):​c.12445_12492del​(p.Ile4149_Thr4164del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000044 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC4 NM_018406.7 inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: 1.06

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 Uncertain_significance. Variant got 2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_018406.7.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC4	NM_018406.7	c.12445_12492del	p.Ile4149_Thr4164del	inframe_deletion	2/25	ENST00000463781.8
MUC4	NM_004532.6	c.83-680_83-633del		intron_variant
MUC4	NM_138297.5	c.83-4830_83-4783del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC4	ENST00000463781.8	c.12445_12492del	p.Ile4149_Thr4164del	inframe_deletion	2/25	5	NM_018406.7	A2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 173 AN: 117380 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.000904

Gnomad AMI AF: 0.00271

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00178

Gnomad EAS AF: 0.00315

Gnomad SAS AF: 0.00162

Gnomad FIN AF: 0.00173

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00155

Gnomad OTH AF: 0.00327

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000436 AC: 57 AN: 1306368 Hom.: 0 AF XY: 0.0000373 AC XY: 24 AN XY: 643900

Gnomad4 AFR exome AF: 0.0000356

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000178

Gnomad4 EAS exome AF: 0.000173

Gnomad4 SAS exome AF: 0.0000267

Gnomad4 FIN exome AF: 0.0000451

Gnomad4 NFE exome AF: 0.0000354

Gnomad4 OTH exome AF: 0.000131

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00146 AC: 172 AN: 117490 Hom.: 0 Cov.: 0 AF XY: 0.00164 AC XY: 94 AN XY: 57438

Gnomad4 AFR AF: 0.000866

Gnomad4 AMR AF: 0.00136

Gnomad4 ASJ AF: 0.00178

Gnomad4 EAS AF: 0.00316

Gnomad4 SAS AF: 0.00162

Gnomad4 FIN AF: 0.00173

Gnomad4 NFE AF: 0.00155

Gnomad4 OTH AF: 0.00321

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

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

- -

Hepatocellular carcinoma 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

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: chr3-195505958;