Genetic Variant MUC4:p.Glu2741Glu (chr3-195783357-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP7

The NM_018406.7(MUC4):c.8223G>A(p.Glu2741Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MUC4
NM_018406.7 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.54

Publications

10 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP7

Synonymous conserved (PhyloP=-3.54 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
MUC4	NM_018406.7 link	c.8223G>A	p.Glu2741Glu	synonymous_variant	Exon 2 of 25	ENST00000463781.8	NP_060876.5
MUC4	NM_004532.6 link	c.83-4902G>A		intron_variant	Intron 1 of 23		NP_004523.3
MUC4	NM_138297.5 link	c.83-9052G>A		intron_variant	Intron 1 of 22		NP_612154.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC4	ENST00000463781.8 link	c.8223G>A	p.Glu2741Glu	synonymous_variant	Exon 2 of 25	5	NM_018406.7	ENSP00000417498.3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

9402

Hom.:

Cov.:

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

333476

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

165828

African (AFR)

AF:

0.00

AC:

AN:

12402

American (AMR)

AF:

0.00

AC:

AN:

7904

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5940

East Asian (EAS)

AF:

0.00

AC:

AN:

9420

South Asian (SAS)

AF:

0.00

AC:

AN:

20922

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10106

Middle Eastern (MID)

AF:

0.00

AC:

AN:

860

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

251754

Other (OTH)

AF:

0.00

AC:

AN:

14168

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

9402

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

4438

African (AFR)

AF:

0.00

AC:

AN:

2850

American (AMR)

AF:

0.00

AC:

AN:

726

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

338

East Asian (EAS)

AF:

0.00

AC:

AN:

318

South Asian (SAS)

AF:

0.00

AC:

AN:

132

European-Finnish (FIN)

AF:

0.00

AC:

AN:

528

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

4302

Other (OTH)

AF:

0.00

AC:

AN:

132

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.2

(source)

DANN

Benign

0.18

PhyloP100

-3.5

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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