Genetic Variant NM_001164462.2:c.1899A>T (chr7-100992462-A-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001164462.2(MUC12):c.1899A>T(p.Thr633Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000816 in 1,537,744 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00056 ( 0 hom., cov: 35)

Exomes 𝑓: 0.00084 ( 16 hom. )

Consequence

MUC12
NM_001164462.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.37

Publications

1 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: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.09).

BP6

Variant 7-100992462-A-T is Benign according to our data. Variant chr7-100992462-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2657801.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.37 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 16 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.1899A>T	p.Thr633Thr	synonymous	Exon 2 of 12	NP_001157934.1	Q9UKN1-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MUC12	ENST00000536621.6	TSL:5 MANE Select	c.1899A>T	p.Thr633Thr	synonymous	Exon 2 of 12	ENSP00000441929.1	Q9UKN1-2
MUC12	ENST00000379442.7	TSL:5	c.2328A>T	p.Thr776Thr	synonymous	Exon 5 of 15	ENSP00000368755.3	Q9UKN1-1
MUC12	ENST00000895813.1		c.68-14009A>T		intron	N/A	ENSP00000565872.1

Frequencies

GnomAD3 genomes

AF:

0.000565

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.00705

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.000959

GnomAD2 exomes

AF:

0.00176

AC:

259

AN:

146910

AF XY:

0.00226

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000568

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00253

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000511

Gnomad OTH exome

AF:

0.00181

GnomAD4 exome

AF:

0.000844

AC:

1170

AN:

1385484

Hom.:

Cov.:

195

AF XY:

0.00114

AC XY:

778

AN XY:

683624

show subpopulations

African (AFR)

AF:

0.0000633

AC:

AN:

31596

American (AMR)

AF:

0.000476

AC:

AN:

35696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25180

East Asian (EAS)

AF:

0.00134

AC:

AN:

35734

South Asian (SAS)

AF:

0.00852

AC:

675

AN:

79192

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35316

Middle Eastern (MID)

AF:

0.00702

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.000278

AC:

300

AN:

1078962

Other (OTH)

AF:

0.00151

AC:

AN:

58108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.413

Heterozygous variant carriers

111

167

222

278

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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

AF:

0.000558

AC:

AN:

152260

Hom.:

Cov.:

AF XY:

0.000752

AC XY:

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41548

American (AMR)

AF:

0.000523

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00116

AC:

AN:

5186

South Asian (SAS)

AF:

0.00706

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000456

AC:

AN:

68014

Other (OTH)

AF:

0.000474

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.410

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000467

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.1

CADD

Benign

1.5

(source)

DANN

Benign

0.15

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism

(source)

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over