rs4679392

Variant names:

• chr3-124927747-A-G
• rs4679392
• NM_033049.4:c.299T>C

Variant summary

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

The NM_033049.4(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. 13/17 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. I100R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.43 (14121 hom., cov: 32)
  • Exomes 𝑓: 0.43 (134242 hom.)
• Consequence: MUC13 NM_033049.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0990
• Publications: 29 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033049.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC13	NM_033049.4	MANE Select	c.299T>C	p.Ile100Thr	missense	Exon 2 of 12	NP_149038.3	Q9H3R2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC13	ENST00000616727.4	TSL:1 MANE Select	c.299T>C	p.Ile100Thr	missense	Exon 2 of 12	ENSP00000485028.1	Q9H3R2
	MUC13	ENST00000891596.1		c.299T>C	p.Ile100Thr	missense	Exon 2 of 12	ENSP00000561655.1
	MUC13	ENST00000891595.1		c.299T>C	p.Ile100Thr	missense	Exon 2 of 10	ENSP00000561654.1

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

GnomAD2 exomes AF: 0.426 AC: 106577 AN: 250278 AF XY: 0.429

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 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

African (AFR) AF: 0.445 AC: 14832 AN: 33342

American (AMR) AF: 0.475 AC: 21210 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 10160 AN: 26136

East Asian (EAS) AF: 0.266 AC: 10550 AN: 39698

South Asian (SAS) AF: 0.472 AC: 40735 AN: 86244

European-Finnish (FIN) AF: 0.467 AC: 24913 AN: 53346

Middle Eastern (MID) AF: 0.398 AC: 2295 AN: 5764

European-Non Finnish (NFE) AF: 0.425 AC: 472751 AN: 1111296

Other (OTH) AF: 0.413 AC: 24940 AN: 60336

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

African (AFR) AF: 0.446 AC: 18406 AN: 41250

American (AMR) AF: 0.461 AC: 7039 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1355 AN: 3472

East Asian (EAS) AF: 0.245 AC: 1269 AN: 5170

South Asian (SAS) AF: 0.473 AC: 2275 AN: 4814

European-Finnish (FIN) AF: 0.479 AC: 5036 AN: 10524

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.422 AC: 28701 AN: 67958

Other (OTH) AF: 0.405 AC: 855 AN: 2112

Alfa AF: 0.424 Hom.: 68691

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 v4.9

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
PhyloP100		0.099
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
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: rs4679392; hg19: chr3-124646594; COSMIC: COSV60698893; COSMIC: COSV60698893;