rs10248292

Variant names:

• chr7-100993961-G-A
• rs10248292
• NM_001164462.2:c.3398G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-100993961-G-A
• chr7-100993961-G-C
• chr7-100993961-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001164462.2(MUC12):​c.3398G>A​(p.Arg1133His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00085 (20 hom., cov: 13)
  • Exomes 𝑓: 0.022 (30 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC12 NM_001164462.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.69
• Publications: 7 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00433439).
• BP6: Variant 7-100993961-G-A is Benign according to our data. Variant chr7-100993961-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2657807.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 20 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164462.2. 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
	MUC12	NM_001164462.2	MANE Select	c.3398G>A	p.Arg1133His	missense	Exon 2 of 12	NP_001157934.1	Q9UKN1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC12	ENST00000536621.6	TSL:5 MANE Select	c.3398G>A	p.Arg1133His	missense	Exon 2 of 12	ENSP00000441929.1	Q9UKN1-2
	MUC12	ENST00000379442.7	TSL:5	c.3827G>A	p.Arg1276His	missense	Exon 5 of 15	ENSP00000368755.3	Q9UKN1-1
	MUC12	ENST00000895813.1		c.68-12510G>A		intron	N/A	ENSP00000565872.1

Frequencies

GnomAD3 genomes AF: 0.000847 AC: 78 AN: 92058 Hom.: 20 Cov.: 13

Gnomad AFR AF: 0.00240

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000341

Gnomad OTH AF: 0.00222

GnomAD2 exomes AF: 0.000403 AC: 42 AN: 104196 AF XY: 0.000362

Gnomad AFR exome AF: 0.00352

Gnomad AMR exome AF: 0.000240

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000449

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000247

Gnomad OTH exome AF: 0.000645

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0225 AC: 24758 AN: 1102748 Hom.: 30 Cov.: 35 AF XY: 0.0225 AC XY: 12257 AN XY: 544788

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0200 AC: 527 AN: 26368

American (AMR) AF: 0.00714 AC: 229 AN: 32072

Ashkenazi Jewish (ASJ) AF: 0.0122 AC: 247 AN: 20212

East Asian (EAS) AF: 0.0210 AC: 526 AN: 25070

South Asian (SAS) AF: 0.0243 AC: 1628 AN: 66972

European-Finnish (FIN) AF: 0.0146 AC: 369 AN: 25242

Middle Eastern (MID) AF: 0.00751 AC: 33 AN: 4394

European-Non Finnish (NFE) AF: 0.0237 AC: 20328 AN: 856684

Other (OTH) AF: 0.0190 AC: 871 AN: 45734

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000846 AC: 78 AN: 92166 Hom.: 20 Cov.: 13 AF XY: 0.000922 AC XY: 41 AN XY: 44468

African (AFR) AF: 0.00240 AC: 61 AN: 25458

American (AMR) AF: 0.00 AC: 0 AN: 10420

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2290

East Asian (EAS) AF: 0.00 AC: 0 AN: 2626

South Asian (SAS) AF: 0.00 AC: 0 AN: 2700

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5436

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.000341 AC: 14 AN: 41008

Other (OTH) AF: 0.00219 AC: 3 AN: 1372

Alfa AF: 0.000457 Hom.: 0

ExAC AF: 0.000852 AC: 15

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.2
DANN	Benign	0.41
DEOGEN2	Benign	0.0046	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.00033	N
LIST_S2	Benign	0.34	T
MetaRNN	Benign	0.0043	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.0	N
PhyloP100		-1.7
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.19	N
REVEL	Benign	0.0020
Sift	Benign	1.0	T
Sift4G	Benign	0.18	T
Vest4		0.013
MVP		0.014
ClinPred		0.0048	T
GERP RS		-1.4
Varity_R		0.028
gMVP		0.0013
Mutation Taster		=100/0	polymorphism

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: rs10248292; hg19: chr7-100637242; COSMIC: COSV65189288;