rs79635145

Positions:

• chr7-101004258-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001164462.2(MUC12):​c.13695C>T​(p.Ser4565=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.57 (473 hom., cov: 3)
  • Exomes 𝑓: 0.64 (83552 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC12 NM_001164462.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.91

Genes affected

MUC12 (HGNC:7510): (mucin 12, cell surface associated) This gene encodes an integral membrane glycoprotein that is a member of the mucin family. Mucins are O-glycosylated proteins that play an essential role in forming protective mucous barriers on epithelial surfaces and have been implicated in epithelial renewal and differentiation. These glycoproteins also play a role in intracellular signaling. This protein is expressed on the apical membrane surface of epithelial cells that line the mucosal surfaces of many different tissues including the colon, pancreas, prostate, and uterus. The expression of this gene is downregulated in colorectal cancer tissue. [provided by RefSeq, Apr 2017]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 7-101004258-C-T is Benign according to our data. Variant chr7-101004258-C-T is described in ClinVar as [Benign]. Clinvar id is 403116.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.91 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC12	NM_001164462.2	c.13695C>T	p.Ser4565=	synonymous_variant	2/12	ENST00000536621.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC12	ENST00000536621.6	c.13695C>T	p.Ser4565=	synonymous_variant	2/12	5	NM_001164462.2	A2
MUC12	ENST00000379442.7	c.14124C>T	p.Ser4708=	synonymous_variant	5/15	5		P4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1191 AN: 2086 Hom.: 473 Cov.: 3 FAILED QC

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.636

GnomAD3 exomes AF: 0.751 AC: 40691 AN: 54170 Hom.: 15365 AF XY: 0.752 AC XY: 20455 AN XY: 27194

Gnomad AFR exome AF: 0.736

Gnomad AMR exome AF: 0.792

Gnomad ASJ exome AF: 0.744

Gnomad EAS exome AF: 0.815

Gnomad SAS exome AF: 0.721

Gnomad FIN exome AF: 0.684

Gnomad NFE exome AF: 0.723

Gnomad OTH exome AF: 0.761

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.636 AC: 283155 AN: 445316 Hom.: 83552 Cov.: 7 AF XY: 0.636 AC XY: 143557 AN XY: 225548

Gnomad4 AFR exome AF: 0.671

Gnomad4 AMR exome AF: 0.740

Gnomad4 ASJ exome AF: 0.673

Gnomad4 EAS exome AF: 0.773

Gnomad4 SAS exome AF: 0.611

Gnomad4 FIN exome AF: 0.636

Gnomad4 NFE exome AF: 0.617

Gnomad4 OTH exome AF: 0.662

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.572 AC: 1193 AN: 2084 Hom.: 473 Cov.: 3 AF XY: 0.563 AC XY: 526 AN XY: 934

Gnomad4 AFR AF: 0.585

Gnomad4 AMR AF: 0.695

Gnomad4 ASJ AF: 0.609

Gnomad4 EAS AF: 0.778

Gnomad4 SAS AF: 0.653

Gnomad4 FIN AF: 0.500

Gnomad4 NFE AF: 0.538

Gnomad4 OTH AF: 0.625

Alfa AF: 0.711 Hom.: 3380

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

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: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.6
DANN	Benign	0.19

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: rs79635145; hg19: chr7-100647539; COSMIC: COSV65183822;