rs2688513

Variant names:

• chr3-195778793-G-A
• rs2688513
• NM_018406.7:c.12787C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-195778793-G-A
• chr3-195778793-G-C
• chr3-195778793-G-T

Variant summary

Our verdict is Benign. The variant received -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. 14/19 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
• Publications: 43 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=1.3717464E-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 rank	MANE	Protein	UniProt
MUC4	NM_018406.7	c.12787C>T	p.Pro4263Ser	missense_variant	Exon 2 of 25	ENST00000463781.8	NP_060876.5
MUC4	NM_004532.6	c.83-338C>T		intron_variant	Intron 1 of 23		NP_004523.3
MUC4	NM_138297.5	c.83-4488C>T		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.12787C>T	p.Pro4263Ser	missense_variant	Exon 2 of 25	5	NM_018406.7	ENSP00000417498.3

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

GnomAD2 exomes AF: 0.788 AC: 174299 AN: 221232 AF XY: 0.787

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 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

African (AFR) AF: 0.974 AC: 29539 AN: 30334

American (AMR) AF: 0.642 AC: 27901 AN: 43446

Ashkenazi Jewish (ASJ) AF: 0.865 AC: 22341 AN: 25832

East Asian (EAS) AF: 0.812 AC: 32118 AN: 39562

South Asian (SAS) AF: 0.678 AC: 57457 AN: 84710

European-Finnish (FIN) AF: 0.776 AC: 40455 AN: 52144

Middle Eastern (MID) AF: 0.841 AC: 4789 AN: 5694

European-Non Finnish (NFE) AF: 0.827 AC: 903559 AN: 1092894

Other (OTH) AF: 0.826 AC: 49100 AN: 59446

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

African (AFR) AF: 0.967 AC: 40171 AN: 41548

American (AMR) AF: 0.723 AC: 11052 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.864 AC: 2998 AN: 3470

East Asian (EAS) AF: 0.802 AC: 4146 AN: 5170

South Asian (SAS) AF: 0.688 AC: 3316 AN: 4822

European-Finnish (FIN) AF: 0.781 AC: 8277 AN: 10604

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.821 AC: 55859 AN: 68006

Other (OTH) AF: 0.858 AC: 1813 AN: 2114

Alfa AF: 0.837 Hom.: 108414

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
AlphaMissense	Benign	0.051
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
PhyloP100		0.29
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
Mutation Taster		=98/2	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: rs2688513; hg19: chr3-195505664; COSMIC: COSV57769812;