chr7-100991613-G-A

Variant names:

• chr7-100991613-G-A
• rs752727121
• NM_001164462.2:c.1050G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001164462.2(MUC12):​c.1050G>A​(p.Ala350Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000425 in 1,302,494 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00089 (0 hom., cov: 28)
  • Exomes 𝑓: 0.00043 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC12 NM_001164462.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.42
• Publications: 0 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 7-100991613-G-A is Benign according to our data. Variant chr7-100991613-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3770855.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.42 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 2 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.1050G>A	p.Ala350Ala	synonymous	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.1050G>A	p.Ala350Ala	synonymous	Exon 2 of 12	ENSP00000441929.1	Q9UKN1-2
	MUC12	ENST00000379442.7	TSL:5	c.1479G>A	p.Ala493Ala	synonymous	Exon 5 of 15	ENSP00000368755.3	Q9UKN1-1
	MUC12	ENST00000895813.1		c.68-14858G>A		intron	N/A	ENSP00000565872.1

Frequencies

GnomAD3 genomes AF: 0.000893 AC: 86 AN: 96352 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.000191

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000291

Gnomad ASJ AF: 0.00411

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000370

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00962

Gnomad NFE AF: 0.00171

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0344 AC: 3425 AN: 99508 AF XY: 0.0325

Gnomad AFR exome AF: 0.0149

Gnomad AMR exome AF: 0.0244

Gnomad ASJ exome AF: 0.0282

Gnomad EAS exome AF: 0.0986

Gnomad FIN exome AF: 0.00743

Gnomad NFE exome AF: 0.0405

Gnomad OTH exome AF: 0.0552

GnomAD4 exome AF: 0.000425 AC: 554 AN: 1302494 Hom.: 2 Cov.: 124 AF XY: 0.000478 AC XY: 306 AN XY: 640142

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

African (AFR) AF: 0.0000650 AC: 2 AN: 30752

American (AMR) AF: 0.000297 AC: 10 AN: 33670

Ashkenazi Jewish (ASJ) AF: 0.00212 AC: 47 AN: 22160

East Asian (EAS) AF: 0.000166 AC: 5 AN: 30164

South Asian (SAS) AF: 0.000526 AC: 38 AN: 72240

European-Finnish (FIN) AF: 0.000135 AC: 4 AN: 29618

Middle Eastern (MID) AF: 0.000558 AC: 3 AN: 5372

European-Non Finnish (NFE) AF: 0.000387 AC: 397 AN: 1025110

Other (OTH) AF: 0.000899 AC: 48 AN: 53408

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.000892 AC: 86 AN: 96464 Hom.: 0 Cov.: 28 AF XY: 0.000759 AC XY: 36 AN XY: 47418

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

African (AFR) AF: 0.000191 AC: 6 AN: 31458

American (AMR) AF: 0.000291 AC: 3 AN: 10324

Ashkenazi Jewish (ASJ) AF: 0.00411 AC: 8 AN: 1948

East Asian (EAS) AF: 0.00 AC: 0 AN: 2798

South Asian (SAS) AF: 0.000371 AC: 1 AN: 2692

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6446

Middle Eastern (MID) AF: 0.0101 AC: 2 AN: 198

European-Non Finnish (NFE) AF: 0.00171 AC: 66 AN: 38638

Other (OTH) AF: 0.00 AC: 0 AN: 1358

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0998 Hom.: 2

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
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.76
DANN	Benign	0.40
PhyloP100		-3.4
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: rs752727121; hg19: chr7-100634894; COSMIC: COSV65182850;