dbSNP rs79635145: MUC12:p.Ser4565Ser (chr7-101004258-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_001164462.2(MUC12):c.13695C>T(p.Ser4565Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 473 hom., cov: 3)

Exomes 𝑓: 0.64 ( 83552 hom. )

Failed GnomAD Quality Control

Consequence

MUC12
NM_001164462.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.91

Publications

2 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:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001164462.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant 7-101004258-C-T is Benign according to our data. Variant chr7-101004258-C-T is described in ClinVar as Benign. ClinVar VariationId is 403116.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.91 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC12	NM_001164462.2	MANE Select	c.13695C>T	p.Ser4565Ser	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.13695C>T	p.Ser4565Ser	synonymous	Exon 2 of 12	ENSP00000441929.1	Q9UKN1-2
MUC12	ENST00000379442.7	TSL:5	c.14124C>T	p.Ser4708Ser	synonymous	Exon 5 of 15	ENSP00000368755.3	Q9UKN1-1
MUC12	ENST00000895813.1		c.68-2213C>T		intron	N/A	ENSP00000565872.1

Frequencies

GnomAD3 genomes

AF:

0.571

AC:

1191

AN:

2086

Hom.:

473

Cov.:

show subpopulations

Gnomad AFR

AF:

0.582

Gnomad AMI

AF:

0.556

Gnomad AMR

AF:

0.690

Gnomad ASJ

AF:

0.609

Gnomad EAS

AF:

0.778

Gnomad SAS

AF:

0.637

Gnomad FIN

AF:

0.500

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.538

Gnomad OTH

AF:

0.636

GnomAD2 exomes

AF:

0.751

AC:

40691

AN:

54170

AF XY:

0.752

show subpopulations

Gnomad AFR exome

AF:

0.736

Gnomad AMR exome

AF:

0.792

Gnomad ASJ exome

AF:

0.744

Gnomad EAS exome

AF:

0.815

Gnomad FIN exome

AF:

0.684

Gnomad NFE exome

AF:

0.723

Gnomad OTH exome

AF:

0.761

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.636

AC:

283155

AN:

445316

Hom.:

83552

Cov.:

AF XY:

0.636

AC XY:

143557

AN XY:

225548

show subpopulations

African (AFR)

AF:

0.671

AC:

8409

AN:

12538

American (AMR)

AF:

0.740

AC:

10375

AN:

14014

Ashkenazi Jewish (ASJ)

AF:

0.673

AC:

7835

AN:

11636

East Asian (EAS)

AF:

0.773

AC:

19178

AN:

24800

South Asian (SAS)

AF:

0.611

AC:

15623

AN:

25588

European-Finnish (FIN)

AF:

0.636

AC:

13871

AN:

21816

Middle Eastern (MID)

AF:

0.718

AC:

1263

AN:

1760

European-Non Finnish (NFE)

AF:

0.617

AC:

190958

AN:

309550

Other (OTH)

AF:

0.662

AC:

15643

AN:

23614

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.546

Heterozygous variant carriers

4183

8365

12548

16730

20913

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3106

6212

9318

12424

15530

<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: AS_VQSR

AF:

0.572

AC:

1193

AN:

2084

Hom.:

473

Cov.:

AF XY:

0.563

AC XY:

526

AN XY:

934

show subpopulations

African (AFR)

AF:

0.585

AC:

242

AN:

414

American (AMR)

AF:

0.695

AC:

132

AN:

190

Ashkenazi Jewish (ASJ)

AF:

0.609

AC:

AN:

East Asian (EAS)

AF:

0.778

AC:

AN:

South Asian (SAS)

AF:

0.653

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

123

AN:

246

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.538

AC:

526

AN:

978

Other (OTH)

AF:

0.625

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.556

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.711

Hom.:

3380

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

1.6

(source)

DANN

Benign

0.19

PhyloP100

-3.9

Mutation Taster

=100/0

polymorphism (auto)

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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