Genetic Variant NM_001164462.2:c.13704G>A (chr7-101004267-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP7

The NM_001164462.2(MUC12):c.13704G>A(p.Leu4568Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 3)

Exomes 𝑓: 0.0000019 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MUC12
NM_001164462.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.33

Publications

4 publications found

Variant links:

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]

MUC12 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.03).

BP7

Synonymous conserved (PhyloP=-1.34 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC12	NM_001164462.2	MANE Select	c.13704G>A	p.Leu4568Leu	synonymous	Exon 2 of 12	NP_001157934.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MUC12	ENST00000536621.6	TSL:5 MANE Select	c.13704G>A	p.Leu4568Leu	synonymous	Exon 2 of 12	ENSP00000441929.1
MUC12	ENST00000379442.7	TSL:5	c.14133G>A	p.Leu4711Leu	synonymous	Exon 5 of 15	ENSP00000368755.3
MUC12	ENST00000895813.1		c.68-2204G>A		intron	N/A	ENSP00000565872.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

4224

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000186

AC:

AN:

537448

Hom.:

Cov.:

AF XY:

0.00000367

AC XY:

AN XY:

272340

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

14138

American (AMR)

AF:

0.00

AC:

AN:

17560

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13214

East Asian (EAS)

AF:

0.0000374

AC:

AN:

26706

South Asian (SAS)

AF:

0.00

AC:

AN:

35662

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24976

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2048

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

375696

Other (OTH)

AF:

0.00

AC:

AN:

27448

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

4224

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

1856

African (AFR)

AF:

0.00

AC:

AN:

788

American (AMR)

AF:

0.00

AC:

AN:

374

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

130

East Asian (EAS)

AF:

0.00

AC:

AN:

136

South Asian (SAS)

AF:

0.00

AC:

AN:

156

European-Finnish (FIN)

AF:

0.00

AC:

AN:

444

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

2112

Other (OTH)

AF:

0.00

AC:

AN:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.38

(source)

DANN

Benign

0.35

PhyloP100

-1.3

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over