7-101004836-C-G

Variant names:

• chr7-101004836-C-G
• rs11766125
• NM_001164462.2:c.14273C>G

Variant summary

Our verdict is Benign. The variant received -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. 13/21 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
• Publications: 22 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MUC12	NM_001164462.2	c.14273C>G	p.Thr4758Arg	missense_variant	Exon 2 of 12	ENST00000536621.6	NP_001157934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC12	ENST00000536621.6	c.14273C>G	p.Thr4758Arg	missense_variant	Exon 2 of 12	5	NM_001164462.2	ENSP00000441929.1
MUC12	ENST00000379442.7	c.14702C>G	p.Thr4901Arg	missense_variant	Exon 5 of 15	5		ENSP00000368755.3

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

GnomAD2 exomes AF: 0.483 AC: 70743 AN: 146590 AF XY: 0.487

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 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

African (AFR) AF: 0.390 AC: 12325 AN: 31592

American (AMR) AF: 0.368 AC: 13154 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 12628 AN: 25182

East Asian (EAS) AF: 0.597 AC: 21325 AN: 35736

South Asian (SAS) AF: 0.492 AC: 38985 AN: 79234

European-Finnish (FIN) AF: 0.504 AC: 17774 AN: 35296

Middle Eastern (MID) AF: 0.431 AC: 2455 AN: 5700

European-Non Finnish (NFE) AF: 0.522 AC: 563221 AN: 1079018

Other (OTH) AF: 0.508 AC: 29529 AN: 58092

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

African (AFR) AF: 0.383 AC: 15868 AN: 41406

American (AMR) AF: 0.390 AC: 5951 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 1741 AN: 3470

East Asian (EAS) AF: 0.603 AC: 3105 AN: 5150

South Asian (SAS) AF: 0.498 AC: 2391 AN: 4806

European-Finnish (FIN) AF: 0.503 AC: 5289 AN: 10522

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.519 AC: 35259 AN: 67942

Other (OTH) AF: 0.453 AC: 956 AN: 2110

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;.
PhyloP100		0.60
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
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: rs11766125; hg19: chr7-100648117; COSMIC: COSV65188235;