Genetic Variant NM_018406.7:c.5879C>T (chr3-195785701-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018406.7(MUC4):c.5879C>T(p.Ser1960Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000793 in 1,260,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 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: 𝑓 0.0 ( 0 hom., cov: 50)

Exomes 𝑓: 7.9e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MUC4
NM_018406.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.02

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.035728008).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC4	NM_018406.7 link	c.5879C>T	p.Ser1960Leu	missense_variant	Exon 2 of 25	ENST00000463781.8	NP_060876.5	Q99102-1E9PDY6
MUC4	NM_004532.6 link	c.83-7246C>T		intron_variant	Intron 1 of 23		NP_004523.3	Q99102-13A0T3F4
MUC4	NM_138297.5 link	c.83-11396C>T		intron_variant	Intron 1 of 22		NP_612154.2	Q99102-12A0T3F4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC4	ENST00000463781.8 link	c.5879C>T	p.Ser1960Leu	missense_variant	Exon 2 of 25	5	NM_018406.7	ENSP00000417498.3		Q99102-1E9PDY6

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

140064

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

7.93e-7

AC:

AN:

1260436

Hom.:

Cov.:

251

AF XY:

0.00

AC XY:

AN XY:

622934

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000102

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

140160

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

68720

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000220

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.94

Eigen

Benign

-0.97

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.011

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.0014

MetaRNN

Benign

0.036

T;T

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.070

N;N

REVEL

Benign

0.020

Sift

Benign

0.049

D;D

Sift4G

Benign

1.0

T;T

Vest4

0.097

MutPred

0.20

Loss of glycosylation at S1960 (P = 0.0051);Loss of glycosylation at S1960 (P = 0.0051);

MVP

0.030

ClinPred

0.083

GERP RS

-0.041

gMVP

0.00020

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over