7-101004267-G-C

Position:

• chr7-101004267-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_001164462.2(MUC12):​c.13704G>C​(p.Leu4568Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (1120 hom., cov: 3)
  • Exomes 𝑓: 0.64 (102340 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC12 NM_001164462.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.33

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.3845177E-4).
• BP6: Variant 7-101004267-G-C is Benign according to our data. Variant chr7-101004267-G-C is described in ClinVar as [Benign]. Clinvar id is 403117.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC12	NM_001164462.2	c.13704G>C	p.Leu4568Phe	missense_variant	2/12	ENST00000536621.6	NP_001157934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC12	ENST00000536621.6	c.13704G>C	p.Leu4568Phe	missense_variant	2/12	5	NM_001164462.2	ENSP00000441929.1
MUC12	ENST00000379442.7	c.14133G>C	p.Leu4711Phe	missense_variant	5/15	5		ENSP00000368755.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 2752 AN: 4222 Hom.: 1116 Cov.: 3 FAILED QC

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.714

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.705

GnomAD3 exomes AF: 0.757 AC: 45942 AN: 60668 Hom.: 17340 AF XY: 0.755 AC XY: 23048 AN XY: 30510

Gnomad AFR exome AF: 0.800

Gnomad AMR exome AF: 0.792

Gnomad ASJ exome AF: 0.743

Gnomad EAS exome AF: 0.816

Gnomad SAS exome AF: 0.718

Gnomad FIN exome AF: 0.670

Gnomad NFE exome AF: 0.725

Gnomad OTH exome AF: 0.766

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.640 AC: 341410 AN: 533038 Hom.: 102340 Cov.: 8 AF XY: 0.641 AC XY: 173015 AN XY: 270062

Gnomad4 AFR exome AF: 0.720

Gnomad4 AMR exome AF: 0.742

Gnomad4 ASJ exome AF: 0.674

Gnomad4 EAS exome AF: 0.780

Gnomad4 SAS exome AF: 0.608

Gnomad4 FIN exome AF: 0.635

Gnomad4 NFE exome AF: 0.622

Gnomad4 OTH exome AF: 0.669

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.652 AC: 2766 AN: 4242 Hom.: 1120 Cov.: 3 AF XY: 0.651 AC XY: 1222 AN XY: 1876

Gnomad4 AFR AF: 0.681

Gnomad4 AMR AF: 0.737

Gnomad4 ASJ AF: 0.715

Gnomad4 EAS AF: 0.812

Gnomad4 SAS AF: 0.664

Gnomad4 FIN AF: 0.597

Gnomad4 NFE AF: 0.620

Gnomad4 OTH AF: 0.682

Alfa AF: 0.474 Hom.: 422

ExAC AF: 0.468 AC: 3710

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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 -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.15
DANN	Benign	0.12
DEOGEN2	Benign	0.0030	T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.00043	N
LIST_S2	Benign	0.24	T;T
MetaRNN	Benign	0.00044	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.1	L;.
PrimateAI	Benign	0.48	T
PROVEAN	Benign	0.020	N;N
REVEL	Benign	0.031
Sift	Uncertain	0.024	D;D
Sift4G	Uncertain	0.057	T;T
Vest4		0.011
MutPred		0.12		.;Gain of phosphorylation at T4566 (P = 0.13);
ClinPred		0.0054	T
GERP RS		-1.8
Varity_R		0.043
gMVP		0.0012

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: rs73402837; hg19: chr7-100647548; COSMIC: COSV65183830;