3-195779036-TGCTGGTGACAGGAAGAGGGGTGCCGTGACCTGTGGACACTGAGGAAGC-T

Variant summary

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

The NM_018406.7(MUC4):c.12496_12543del(p.Ala4166_Ser4181del) 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 0.018 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00024 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC4 NM_018406.7 inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: 0.316

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.12496_12543del	p.Ala4166_Ser4181del	inframe_deletion	2/25	ENST00000463781.8
MUC4	NM_004532.6	c.83-629_83-582del		intron_variant
MUC4	NM_138297.5	c.83-4779_83-4732del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC4	ENST00000463781.8	c.12496_12543del	p.Ala4166_Ser4181del	inframe_deletion	2/25	5	NM_018406.7	A2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 510 AN: 27568 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.00796

Gnomad AMI AF: 0.0172

Gnomad AMR AF: 0.0168

Gnomad ASJ AF: 0.0347

Gnomad EAS AF: 0.0451

Gnomad SAS AF: 0.0145

Gnomad FIN AF: 0.0304

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0199

Gnomad OTH AF: 0.0254

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000237 AC: 134 AN: 566012 Hom.: 0 AF XY: 0.000225 AC XY: 63 AN XY: 280260

Gnomad4 AFR exome AF: 0.000338

Gnomad4 AMR exome AF: 0.000143

Gnomad4 ASJ exome AF: 0.000951

Gnomad4 EAS exome AF: 0.00172

Gnomad4 SAS exome AF: 0.000145

Gnomad4 FIN exome AF: 0.000624

Gnomad4 NFE exome AF: 0.000180

Gnomad4 OTH exome AF: 0.000354

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0185 AC: 510 AN: 27612 Hom.: 0 Cov.: 0 AF XY: 0.0199 AC XY: 266 AN XY: 13386

Gnomad4 AFR AF: 0.00793

Gnomad4 AMR AF: 0.0167

Gnomad4 ASJ AF: 0.0347

Gnomad4 EAS AF: 0.0450

Gnomad4 SAS AF: 0.0143

Gnomad4 FIN AF: 0.0304

Gnomad4 NFE AF: 0.0199

Gnomad4 OTH AF: 0.0253

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs748705487; hg19: chr3-195505907;