dbSNP rs2259292: MUC4:p.Gly4324Val (chr3-195774278-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018406.7(MUC4):c.12971G>T(p.Gly4324Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,428,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

MUC4
NM_018406.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.79

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.088332295).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
MUC4	NM_018406.7 link	c.12971G>T	p.Gly4324Val	missense_variant	Exon 4 of 25	ENST00000463781.8	NP_060876.5
MUC4	NM_004532.6 link	c.263G>T	p.Gly88Val	missense_variant	Exon 3 of 24		NP_004523.3
MUC4	NM_138297.5 link	c.110G>T	p.Gly37Val	missense_variant	Exon 2 of 23		NP_612154.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC4	ENST00000463781.8 link	c.12971G>T	p.Gly4324Val	missense_variant	Exon 4 of 25	5	NM_018406.7	ENSP00000417498.3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.00e-7

AC:

AN:

1428756

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

709246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31648

American (AMR)

AF:

0.00

AC:

AN:

39412

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24186

East Asian (EAS)

AF:

0.00

AC:

AN:

38196

South Asian (SAS)

AF:

0.0000122

AC:

AN:

81744

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51856

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5520

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1097278

Other (OTH)

AF:

0.00

AC:

AN:

58916

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

1.5

(source)

DANN

Benign

0.85

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.31

T;T;T;T

M_CAP

Benign

0.037

MetaRNN

Benign

0.088

T;T;T;T

MetaSVM

Benign

-1.1

PhyloP100

-1.8

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-2.4

N;N;N;N

REVEL

Benign

0.19

Sift

Benign

0.20

T;T;T;T

Sift4G

Benign

0.22

T;T;T;T

Polyphen

0.040

B;B;.;.

Vest4

0.21

MVP

0.12

ClinPred

0.12

GERP RS

-2.1

gMVP

0.27

Mutation Taster

=98/2

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over