rs2688513

chr3-195778793-G-Achr3-195778793-G-Cchr3-195778793-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018406.7(MUC4):c.12787C>T(p.Pro4263Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.817 in 1,586,280 control chromosomes in the GnomAD database, including 533,070 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 0.84 (54969 hom., cov: 34)
  • Exomes 𝑓: 0.81 (478101 hom.)
• Consequence: MUC4 NM_018406.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.294

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=1.3717464E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC4	NM_018406.7	c.12787C>T	p.Pro4263Ser	missense_variant	2/25	ENST00000463781.8
MUC4	NM_004532.6	c.83-338C>T		intron_variant
MUC4	NM_138297.5	c.83-4488C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC4	ENST00000463781.8	c.12787C>T	p.Pro4263Ser	missense_variant	2/25	5	NM_018406.7	A2

Frequencies

GnomAD3 genomes AF: 0.845 AC: 128469 AN: 152100 Hom.: 54916 Cov.: 34

Gnomad AFR AF: 0.967

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.724

Gnomad ASJ AF: 0.864

Gnomad EAS AF: 0.803

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.781

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.821

Gnomad OTH AF: 0.856

GnomAD3 exomes AF: 0.788 AC: 174299 AN: 221232 Hom.: 70169 AF XY: 0.787 AC XY: 94580 AN XY: 120188

Gnomad AFR exome AF: 0.968

Gnomad AMR exome AF: 0.636

Gnomad ASJ exome AF: 0.869

Gnomad EAS exome AF: 0.807

Gnomad SAS exome AF: 0.676

Gnomad FIN exome AF: 0.784

Gnomad NFE exome AF: 0.832

Gnomad OTH exome AF: 0.804

GnomAD4 exome AF: 0.814 AC: 1167259 AN: 1434062 Hom.: 478101 Cov.: 66 AF XY: 0.810 AC XY: 577988 AN XY: 713274

Gnomad4 AFR exome AF: 0.974

Gnomad4 AMR exome AF: 0.642

Gnomad4 ASJ exome AF: 0.865

Gnomad4 EAS exome AF: 0.812

Gnomad4 SAS exome AF: 0.678

Gnomad4 FIN exome AF: 0.776

Gnomad4 NFE exome AF: 0.827

Gnomad4 OTH exome AF: 0.826

GnomAD4 genome AF: 0.845 AC: 128575 AN: 152218 Hom.: 54969 Cov.: 34 AF XY: 0.838 AC XY: 62367 AN XY: 74430

Gnomad4 AFR AF: 0.967

Gnomad4 AMR AF: 0.723

Gnomad4 ASJ AF: 0.864

Gnomad4 EAS AF: 0.802

Gnomad4 SAS AF: 0.688

Gnomad4 FIN AF: 0.781

Gnomad4 NFE AF: 0.821

Gnomad4 OTH AF: 0.858

Alfa AF: 0.830 Hom.: 72066

Bravo AF: 0.847

TwinsUK AF: 0.830 AC: 3077

ALSPAC AF: 0.826 AC: 3184

ESP6500AA AF: 0.967 AC: 4002

ESP6500EA AF: 0.828 AC: 6897

ExAC AF: 0.789 AC: 94424

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.64
Cadd	Benign	0.13
Dann	Benign	0.30
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.00084	N
LIST_S2	Benign	0.42	T;T
MetaRNN	Benign	0.0000014	T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.70	N;N
REVEL	Benign	0.029
Sift	Benign	1.0	T;T
Sift4G	Benign	0.81	T;T
Vest4		0.054
ClinPred		0.0011	T
GERP RS		0.27
gMVP		0.085

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: rs2688513; hg19: chr3-195505664; COSMIC: COSV57769812;