3-195788723-C-G

Variant names:

• chr3-195788723-C-G
• rs13095016
• NM_018406.7:c.2857G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018406.7(MUC4):​c.2857G>C​(p.Glu953Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 1,610,614 control chromosomes in the GnomAD database, including 527,048 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 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 0.76 (44173 hom., cov: 31)
  • Exomes 𝑓: 0.81 (482875 hom.)
• Consequence: MUC4 NM_018406.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.47
• Publications: 27 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.150274E-6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC4	NM_018406.7	c.2857G>C	p.Glu953Gln	missense_variant	Exon 2 of 25	ENST00000463781.8	NP_060876.5
MUC4	NM_004532.6	c.83-10268G>C		intron_variant	Intron 1 of 23		NP_004523.3
MUC4	NM_138297.5	c.83-14418G>C		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	c.2857G>C	p.Glu953Gln	missense_variant	Exon 2 of 25	5	NM_018406.7	ENSP00000417498.3

Frequencies

GnomAD3 genomes AF: 0.757 AC: 114761 AN: 151628 Hom.: 44147 Cov.: 31

Gnomad AFR AF: 0.638

Gnomad AMI AF: 0.779

Gnomad AMR AF: 0.709

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.794

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.829

Gnomad OTH AF: 0.806

GnomAD2 exomes AF: 0.772 AC: 191014 AN: 247474 AF XY: 0.774

Gnomad AFR exome AF: 0.632

Gnomad AMR exome AF: 0.648

Gnomad ASJ exome AF: 0.868

Gnomad EAS exome AF: 0.811

Gnomad FIN exome AF: 0.796

Gnomad NFE exome AF: 0.837

Gnomad OTH exome AF: 0.799

GnomAD4 exome AF: 0.811 AC: 1182940 AN: 1458868 Hom.: 482875 Cov.: 85 AF XY: 0.808 AC XY: 586292 AN XY: 725744

African (AFR) AF: 0.626 AC: 20648 AN: 32962

American (AMR) AF: 0.653 AC: 29085 AN: 44548

Ashkenazi Jewish (ASJ) AF: 0.872 AC: 22762 AN: 26118

East Asian (EAS) AF: 0.816 AC: 32377 AN: 39676

South Asian (SAS) AF: 0.663 AC: 57067 AN: 86020

European-Finnish (FIN) AF: 0.795 AC: 42370 AN: 53274

Middle Eastern (MID) AF: 0.821 AC: 4733 AN: 5764

European-Non Finnish (NFE) AF: 0.833 AC: 925227 AN: 1110342

Other (OTH) AF: 0.809 AC: 48671 AN: 60164

GnomAD4 genome AF: 0.757 AC: 114831 AN: 151746 Hom.: 44173 Cov.: 31 AF XY: 0.753 AC XY: 55856 AN XY: 74170

African (AFR) AF: 0.638 AC: 26300 AN: 41214

American (AMR) AF: 0.709 AC: 10812 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.870 AC: 3022 AN: 3472

East Asian (EAS) AF: 0.805 AC: 4137 AN: 5138

South Asian (SAS) AF: 0.665 AC: 3202 AN: 4812

European-Finnish (FIN) AF: 0.794 AC: 8415 AN: 10594

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.829 AC: 56300 AN: 67946

Other (OTH) AF: 0.809 AC: 1705 AN: 2108

Alfa AF: 0.810 Hom.: 12775

Bravo AF: 0.744

TwinsUK AF: 0.836 AC: 3100

ALSPAC AF: 0.831 AC: 3203

ESP6500AA AF: 0.655 AC: 2854

ESP6500EA AF: 0.831 AC: 7071

ExAC AF: 0.773 AC: 93712

Asia WGS AF: 0.779 AC: 2711 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.13
DANN	Benign	0.53
Eigen	Benign	-0.81
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0037	N
LIST_S2	Benign	0.47	T;T
MetaRNN	Benign	0.0000012	T;T
MetaSVM	Benign	-0.86	T
PhyloP100		-2.5
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.10	N;N
REVEL	Benign	0.080
Sift	Benign	1.0	T;T
Sift4G	Benign	0.38	T;T
Vest4		0.024
ClinPred		0.019	T
GERP RS		-2.6
gMVP		0.0032
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13095016; hg19: chr3-195515594; COSMIC: COSV107442910;