rs11766125

Positions:

• chr7-101004836-C-G

Variant summary

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

The NM_001164462.2(MUC12):​c.14273C>G​(p.Thr4758Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 1,537,424 control chromosomes in the GnomAD database, including 201,039 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 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 0.47 (16967 hom., cov: 31)
  • Exomes 𝑓: 0.51 (184072 hom.)
• Consequence: MUC12 NM_001164462.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.604

Genes affected

MUC12 (HGNC:7510): (mucin 12, cell surface associated) This gene encodes an integral membrane glycoprotein that is a member of the mucin family. Mucins are O-glycosylated proteins that play an essential role in forming protective mucous barriers on epithelial surfaces and have been implicated in epithelial renewal and differentiation. These glycoproteins also play a role in intracellular signaling. This protein is expressed on the apical membrane surface of epithelial cells that line the mucosal surfaces of many different tissues including the colon, pancreas, prostate, and uterus. The expression of this gene is downregulated in colorectal cancer tissue. [provided by RefSeq, Apr 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.4604191E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC12	NM_001164462.2	c.14273C>G	p.Thr4758Arg	missense_variant	2/12	ENST00000536621.6	NP_001157934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC12	ENST00000536621.6	c.14273C>G	p.Thr4758Arg	missense_variant	2/12	5	NM_001164462.2	ENSP00000441929	A2
MUC12	ENST00000379442.7	c.14702C>G	p.Thr4901Arg	missense_variant	5/15	5		ENSP00000368755	P4

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71085 AN: 151752 Hom.: 16968 Cov.: 31

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.455

GnomAD3 exomes AF: 0.483 AC: 70743 AN: 146590 Hom.: 17435 AF XY: 0.487 AC XY: 37906 AN XY: 77788

Gnomad AFR exome AF: 0.386

Gnomad AMR exome AF: 0.371

Gnomad ASJ exome AF: 0.503

Gnomad EAS exome AF: 0.602

Gnomad SAS exome AF: 0.487

Gnomad FIN exome AF: 0.509

Gnomad NFE exome AF: 0.512

Gnomad OTH exome AF: 0.493

GnomAD4 exome AF: 0.513 AC: 711396 AN: 1385554 Hom.: 184072 Cov.: 78 AF XY: 0.513 AC XY: 351029 AN XY: 683670

Gnomad4 AFR exome AF: 0.390

Gnomad4 AMR exome AF: 0.368

Gnomad4 ASJ exome AF: 0.501

Gnomad4 EAS exome AF: 0.597

Gnomad4 SAS exome AF: 0.492

Gnomad4 FIN exome AF: 0.504

Gnomad4 NFE exome AF: 0.522

Gnomad4 OTH exome AF: 0.508

GnomAD4 genome AF: 0.468 AC: 71111 AN: 151870 Hom.: 16967 Cov.: 31 AF XY: 0.465 AC XY: 34495 AN XY: 74206

Gnomad4 AFR AF: 0.383

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.502

Gnomad4 EAS AF: 0.603

Gnomad4 SAS AF: 0.498

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.519

Gnomad4 OTH AF: 0.453

Alfa AF: 0.482 Hom.: 3283

Bravo AF: 0.458

TwinsUK AF: 0.523 AC: 1938

ALSPAC AF: 0.519 AC: 2001

ESP6500AA AF: 0.405 AC: 560

ESP6500EA AF: 0.514 AC: 1634

ExAC AF: 0.465 AC: 11226

Asia WGS AF: 0.509 AC: 1770 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.9
DANN	Benign	0.13
DEOGEN2	Benign	0.048	T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0011	N
LIST_S2	Benign	0.21	T;T
MetaRNN	Benign	0.000015	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.7	L;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.011
Sift	Benign	0.48	T;T
Sift4G	Uncertain	0.032	D;D
Vest4		0.021
ClinPred		0.0072	T
GERP RS		-0.98
Varity_R		0.12
gMVP		0.020

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: rs11766125; hg19: chr7-100648117; COSMIC: COSV65188235;