rs4679392

Positions:

• chr3-124927747-A-G

Variant summary

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

The ENST00000616727.4(MUC13):​c.299T>C​(p.Ile100Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 1,612,616 control chromosomes in the GnomAD database, including 148,363 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.43 (14121 hom., cov: 32)
  • Exomes 𝑓: 0.43 (134242 hom.)
• Consequence: MUC13 ENST00000616727.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0990

Genes affected

MUC13 (HGNC:7511): (mucin 13, cell surface associated) Epithelial mucins, such as MUC13, are a family of secreted and cell surface glycoproteins expressed by ductal and glandular epithelial tissues (Williams et al., 2001 [PubMed 11278439]).[supplied by OMIM, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.2903085E-4).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC13	NM_033049.4	c.299T>C	p.Ile100Thr	missense_variant	2/12	ENST00000616727.4	NP_149038.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC13	ENST00000616727.4	c.299T>C	p.Ile100Thr	missense_variant	2/12	1	NM_033049.4	ENSP00000485028	P1
MUC13	ENST00000478191.1	c.53-147T>C		intron_variant		4		ENSP00000418660
MUC13	ENST00000490147.1	n.25T>C		non_coding_transcript_exon_variant	1/4	3

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65398 AN: 151654 Hom.: 14109 Cov.: 32

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.401

GnomAD3 exomes AF: 0.426 AC: 106577 AN: 250278 Hom.: 23276 AF XY: 0.429 AC XY: 58082 AN XY: 135460

Gnomad AFR exome AF: 0.437

Gnomad AMR exome AF: 0.476

Gnomad ASJ exome AF: 0.386

Gnomad EAS exome AF: 0.236

Gnomad SAS exome AF: 0.470

Gnomad FIN exome AF: 0.475

Gnomad NFE exome AF: 0.422

Gnomad OTH exome AF: 0.417

GnomAD4 exome AF: 0.426 AC: 622386 AN: 1460844 Hom.: 134242 Cov.: 49 AF XY: 0.428 AC XY: 310734 AN XY: 726762

Gnomad4 AFR exome AF: 0.445

Gnomad4 AMR exome AF: 0.475

Gnomad4 ASJ exome AF: 0.389

Gnomad4 EAS exome AF: 0.266

Gnomad4 SAS exome AF: 0.472

Gnomad4 FIN exome AF: 0.467

Gnomad4 NFE exome AF: 0.425

Gnomad4 OTH exome AF: 0.413

GnomAD4 genome AF: 0.431 AC: 65461 AN: 151772 Hom.: 14121 Cov.: 32 AF XY: 0.434 AC XY: 32217 AN XY: 74168

Gnomad4 AFR AF: 0.446

Gnomad4 AMR AF: 0.461

Gnomad4 ASJ AF: 0.390

Gnomad4 EAS AF: 0.245

Gnomad4 SAS AF: 0.473

Gnomad4 FIN AF: 0.479

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.405

Alfa AF: 0.422 Hom.: 35151

Bravo AF: 0.429

TwinsUK AF: 0.417 AC: 1546

ALSPAC AF: 0.419 AC: 1615

ESP6500AA AF: 0.453 AC: 1998

ESP6500EA AF: 0.423 AC: 3636

ExAC AF: 0.422 AC: 50570

EpiCase AF: 0.422

EpiControl AF: 0.420

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.35
DANN	Benign	0.33
DEOGEN2	Benign	0.0024	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.000020	N
LIST_S2	Benign	0.24	T
MetaRNN	Benign	0.00023	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.81	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.25	T
Sift4G	Benign	1.0	T
Vest4		0.012
ClinPred		0.0045	T
GERP RS		1.9
Varity_R		0.022
gMVP		0.12

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: rs4679392; hg19: chr3-124646594; COSMIC: COSV60698893; COSMIC: COSV60698893;