Variant 7-100994375-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001164462.2(MUC12):c.3812C>T(p.Pro1271Leu) 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 2)

Exomes 𝑓: 0.0018 ( 454 hom. )

Failed GnomAD Quality Control

Consequence

MUC12
NM_001164462.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0610

Variant links:

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]

MUC12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0043216944).

BP6

Variant 7-100994375-C-T is Benign according to our data. Variant chr7-100994375-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2657809.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC12	NM_001164462.2 linkuse as main transcript	c.3812C>T	p.Pro1271Leu	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 linkuse as main transcript	c.3812C>T	p.Pro1271Leu	missense_variant	2/12	5	NM_001164462.2	ENSP00000441929	A2	Q9UKN1-2
MUC12	ENST00000379442.7 linkuse as main transcript	c.4241C>T	p.Pro1414Leu	missense_variant	5/15	5		ENSP00000368755	P4	Q9UKN1-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

53220

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00173

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00617

Gnomad NFE

AF:

0.000109

Gnomad OTH

AF:

0.00132

GnomAD3 exomes

AF:

0.00129

AC:

106

AN:

82436

Hom.:

AF XY:

0.00178

AC XY:

AN XY:

43348

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000157

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00786

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000163

Gnomad OTH exome

AF:

0.000405

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00176

AC:

1285

AN:

731376

Hom.:

454

Cov.:

AF XY:

0.00242

AC XY:

879

AN XY:

362744

show subpopulations

Gnomad4 AFR exome

AF:

0.000206

Gnomad4 AMR exome

AF:

0.000491

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000188

Gnomad4 SAS exome

AF:

0.0189

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000411

Gnomad4 OTH exome

AF:

0.00306

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000113

AC:

AN:

53264

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

25662

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00174

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000109

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000169

Hom.:

ExAC

AF:

0.00687

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2024

MUC12: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.9

DANN

Benign

0.37

DEOGEN2

Benign

0.0066

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0036

LIST_S2

Benign

0.40

T;T

MetaRNN

Benign

0.0043

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.91

N;N

REVEL

Benign

0.11

Sift

Benign

0.10

T;T

Sift4G

Benign

0.077

T;T

Vest4

0.036

MutPred

0.16

.;Loss of glycosylation at S1272 (P = 0.0885);

MVP

0.076

ClinPred

0.013

GERP RS

-1.4

Varity_R

0.032

gMVP

0.0032

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over