chr3-195781797-GTC-G

Variant names:

• chr3-195781797-GTC-G
• rs757413270
• NM_018406.7:c.9781_9782delGA

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_018406.7(MUC4):​c.9781_9782delGA​(p.Asp3261HisfsTer16) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.070 (3 hom., cov: 0)
  • Exomes 𝑓: 0.21 (500 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC4 NM_018406.7 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.988
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 3-195781797-GTC-G is Benign according to our data. Variant chr3-195781797-GTC-G is described in ClinVar as [Benign]. Clinvar id is 403120.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC4	NM_018406.7	c.9781_9782delGA	p.Asp3261HisfsTer16	frameshift_variant	Exon 2 of 25	ENST00000463781.8	NP_060876.5
MUC4	NM_004532.6	c.83-3344_83-3343delGA		intron_variant	Intron 1 of 23		NP_004523.3
MUC4	NM_138297.5	c.83-7494_83-7493delGA		intron_variant	Intron 1 of 22		NP_612154.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC4	ENST00000463781.8	c.9781_9782delGA	p.Asp3261HisfsTer16	frameshift_variant	Exon 2 of 25	5	NM_018406.7	ENSP00000417498.3

Frequencies

GnomAD3 genomes AF: 0.0699 AC: 3977 AN: 56916 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.0195

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.0656

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.0939

Gnomad FIN AF: 0.0873

Gnomad MID AF: 0.0175

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0601

GnomAD2 exomes AF: 0.0333 AC: 2777 AN: 83354 AF XY: 0.0329

Gnomad AFR exome AF: 0.00574

Gnomad AMR exome AF: 0.0181

Gnomad ASJ exome AF: 0.0552

Gnomad EAS exome AF: 0.0105

Gnomad FIN exome AF: 0.0766

Gnomad NFE exome AF: 0.0369

Gnomad OTH exome AF: 0.0304

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.212 AC: 130452 AN: 614940 Hom.: 500 AF XY: 0.207 AC XY: 61822 AN XY: 299084

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0354 AC: 748 AN: 21156

American (AMR) AF: 0.124 AC: 2022 AN: 16314

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 2018 AN: 7944

East Asian (EAS) AF: 0.161 AC: 937 AN: 5820

South Asian (SAS) AF: 0.122 AC: 4041 AN: 33138

European-Finnish (FIN) AF: 0.123 AC: 1689 AN: 13782

Middle Eastern (MID) AF: 0.131 AC: 249 AN: 1898

European-Non Finnish (NFE) AF: 0.233 AC: 114352 AN: 491098

Other (OTH) AF: 0.185 AC: 4396 AN: 23790

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0698 AC: 3979 AN: 56982 Hom.: 3 Cov.: 0 AF XY: 0.0705 AC XY: 1925 AN XY: 27314

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0195 AC: 404 AN: 20700

American (AMR) AF: 0.0657 AC: 370 AN: 5628

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 135 AN: 932

East Asian (EAS) AF: 0.197 AC: 249 AN: 1262

South Asian (SAS) AF: 0.0922 AC: 148 AN: 1606

European-Finnish (FIN) AF: 0.0873 AC: 262 AN: 3002

Middle Eastern (MID) AF: 0.0189 AC: 2 AN: 106

European-Non Finnish (NFE) AF: 0.102 AC: 2331 AN: 22802

Other (OTH) AF: 0.0625 AC: 42 AN: 672

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.99
Mutation Taster		=200/0	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs757413270; hg19: chr3-195508668; COSMIC: COSV57788134; COSMIC: COSV57788134;