Variant chr3-195750916-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_018406.7(MUC4):c.15844G>A(p.Gly5282Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000914 in 1,613,776 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0048 ( 4 hom., cov: 29)

Exomes 𝑓: 0.00051 ( 3 hom. )

Consequence

MUC4
NM_018406.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.825

Variant links:

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]

MUC4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031014085).

BP6

Variant 3-195750916-C-T is Benign according to our data. Variant chr3-195750916-C-T is described in ClinVar as [Benign]. Clinvar id is 708776.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MUC4	NM_018406.7 linkuse as main transcript	c.15844G>A	p.Gly5282Arg	missense_variant	23/25	ENST00000463781.8
MUC4	NM_004532.6 linkuse as main transcript	c.3136G>A	p.Gly1046Arg	missense_variant	22/24
MUC4	NM_138297.5 linkuse as main transcript	c.2983G>A	p.Gly995Arg	missense_variant	21/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC4	ENST00000463781.8 linkuse as main transcript	c.15844G>A	p.Gly5282Arg	missense_variant	23/25	5	NM_018406.7	A2	Q99102-1

Frequencies

GnomAD3 genomes

AF:

0.00481

AC:

732

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0159

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00386

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00126

AC:

316

AN:

251028

Hom.:

AF XY:

0.000883

AC XY:

120

AN XY:

135832

show subpopulations

Gnomad AFR exome

AF:

0.0154

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000970

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000508

AC:

742

AN:

1461572

Hom.:

Cov.:

AF XY:

0.000463

AC XY:

337

AN XY:

727094

show subpopulations

Gnomad4 AFR exome

AF:

0.0160

Gnomad4 AMR exome

AF:

0.00165

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000315

Gnomad4 OTH exome

AF:

0.00152

GnomAD4 genome

AF:

0.00482

AC:

733

AN:

152204

Hom.:

Cov.:

AF XY:

0.00445

AC XY:

331

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0158

Gnomad4 AMR

AF:

0.00386

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00147

Hom.:

Bravo

AF:

0.00586

ESP6500AA

AF:

0.0143

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00149

AC:

181

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.91

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.00017

LIST_S2

Benign

0.47

T;T;T;T

MetaRNN

Benign

0.0031

T;T;T;T

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

3.7

N;N;N;N

REVEL

Benign

0.028

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0010

B;B;B;B

Vest4

0.14

MutPred

0.23

.;.;Gain of catalytic residue at G5282 (P = 0.0652);.;

MVP

0.014

ClinPred

0.016

GERP RS

2.7

gMVP

0.48

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