3-195779058-GCC-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 8P and 6B. PVS1 BP6_Moderate BS2

The NM_018406.7(MUC4):c.12520_12521del(p.Gly4174HisfsTer15) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.00053 (2 hom., cov: 0)
  • Exomes 𝑓: 0.0017 (9 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC4 NM_018406.7 frameshift
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.771

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.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• BP6: Variant 3-195779058-GCC-G is Benign according to our data. Variant chr3-195779058-GCC-G is described in ClinVar as [Likely_benign]. Clinvar id is 2654380.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC4	NM_018406.7	c.12520_12521del	p.Gly4174HisfsTer15	frameshift_variant	2/25	ENST00000463781.8
MUC4	NM_004532.6	c.83-605_83-604del		intron_variant
MUC4	NM_138297.5	c.83-4755_83-4754del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC4	ENST00000463781.8	c.12520_12521del	p.Gly4174HisfsTer15	frameshift_variant	2/25	5	NM_018406.7	A2

Frequencies

GnomAD3 genomes AF: 0.000519 AC: 67 AN: 129096 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000689

Gnomad ASJ AF: 0.000347

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000250

Gnomad FIN AF: 0.000112

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000275

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000360 AC: 44 AN: 122386 Hom.: 2 AF XY: 0.000342 AC XY: 22 AN XY: 64290

Gnomad AFR exome AF: 0.000963

Gnomad AMR exome AF: 0.000190

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000111

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00165

Gnomad NFE exome AF: 0.000259

Gnomad OTH exome AF: 0.000282

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00170 AC: 1718 AN: 1012510 Hom.: 9 AF XY: 0.00208 AC XY: 1033 AN XY: 497804

Gnomad4 AFR exome AF: 0.00692

Gnomad4 AMR exome AF: 0.00257

Gnomad4 ASJ exome AF: 0.00205

Gnomad4 EAS exome AF: 0.00383

Gnomad4 SAS exome AF: 0.00175

Gnomad4 FIN exome AF: 0.00243

Gnomad4 NFE exome AF: 0.00137

Gnomad4 OTH exome AF: 0.00265

GnomAD4 genome AF: 0.000526 AC: 68 AN: 129202 Hom.: 2 Cov.: 0 AF XY: 0.000588 AC XY: 37 AN XY: 62914

Gnomad4 AFR AF: 0.00113

Gnomad4 AMR AF: 0.000688

Gnomad4 ASJ AF: 0.000347

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000250

Gnomad4 FIN AF: 0.000112

Gnomad4 NFE AF: 0.000275

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

MUC4: BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1464499426; hg19: chr3-195505929;