chr3-195788723-C-G

Position:

• chr3-195788723-C-G

Variant summary

Our verdict is Benign. Variant got -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. 12/16 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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MUC4	NM_018406.7	c.2857G>C	p.Glu953Gln	missense_variant	2/25	ENST00000463781.8	NP_060876.5
MUC4	NM_004532.6	c.83-10268G>C		intron_variant			NP_004523.3
MUC4	NM_138297.5	c.83-14418G>C		intron_variant			NP_612154.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC4	ENST00000463781.8	c.2857G>C	p.Glu953Gln	missense_variant	2/25	5	NM_018406.7	ENSP00000417498	A2

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

GnomAD3 exomes AF: 0.772 AC: 191014 AN: 247474 Hom.: 74832 AF XY: 0.774 AC XY: 104004 AN XY: 134324

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 SAS exome AF: 0.661

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

Gnomad4 AFR exome AF: 0.626

Gnomad4 AMR exome AF: 0.653

Gnomad4 ASJ exome AF: 0.872

Gnomad4 EAS exome AF: 0.816

Gnomad4 SAS exome AF: 0.663

Gnomad4 FIN exome AF: 0.795

Gnomad4 NFE exome AF: 0.833

Gnomad4 OTH exome AF: 0.809

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

Gnomad4 AFR AF: 0.638

Gnomad4 AMR AF: 0.709

Gnomad4 ASJ AF: 0.870

Gnomad4 EAS AF: 0.805

Gnomad4 SAS AF: 0.665

Gnomad4 FIN AF: 0.794

Gnomad4 NFE AF: 0.829

Gnomad4 OTH AF: 0.809

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
MutationTaster	Benign	1.0	P;P;P;P
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

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

Other links and lift over

dbSNP: rs13095016; hg19: chr3-195515594;