Genetic Variant NM_001164462.2:c.5415A>G (chr7-100995978-A-G) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_001164462.2(MUC12):c.5415A>G(p.Thr1805Thr) 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0030 ( 0 hom., cov: 8)

Exomes 𝑓: 0.0059 ( 12 hom. )

Failed GnomAD Quality Control

Consequence

MUC12
NM_001164462.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.34

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

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.08).

BP6

Variant 7-100995978-A-G is Benign according to our data. Variant chr7-100995978-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3025383.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.34 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC12	NM_001164462.2 link	c.5415A>G	p.Thr1805Thr	synonymous_variant	Exon 2 of 12	ENST00000536621.6	NP_001157934.1	Q9UKN1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC12	ENST00000536621.6 link	c.5415A>G	p.Thr1805Thr	synonymous_variant	Exon 2 of 12	5	NM_001164462.2	ENSP00000441929.1		Q9UKN1-2
MUC12	ENST00000379442.7 link	c.5844A>G	p.Thr1948Thr	synonymous_variant	Exon 5 of 15	5		ENSP00000368755.3		Q9UKN1-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

200

AN:

66178

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000953

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00204

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00403

Gnomad MID

AF:

0.00439

Gnomad NFE

AF:

0.00454

Gnomad OTH

AF:

0.00127

GnomAD3 exomes

AF:

0.00374

AC:

243

AN:

65056

Hom.:

AF XY:

0.00383

AC XY:

126

AN XY:

32880

show subpopulations

Gnomad AFR exome

AF:

0.000733

Gnomad AMR exome

AF:

0.00184

Gnomad ASJ exome

AF:

0.00135

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000525

Gnomad FIN exome

AF:

0.00626

Gnomad NFE exome

AF:

0.00784

Gnomad OTH exome

AF:

0.00288

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00585

AC:

4452

AN:

760768

Hom.:

Cov.:

AF XY:

0.00575

AC XY:

2230

AN XY:

388014

show subpopulations

Gnomad4 AFR exome

AF:

0.000989

Gnomad4 AMR exome

AF:

0.00192

Gnomad4 ASJ exome

AF:

0.000733

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000366

Gnomad4 FIN exome

AF:

0.00441

Gnomad4 NFE exome

AF:

0.00761

Gnomad4 OTH exome

AF:

0.00370

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00302

AC:

200

AN:

66244

Hom.:

Cov.:

AF XY:

0.00273

AC XY:

AN XY:

29670

show subpopulations

Gnomad4 AFR

AF:

0.000948

Gnomad4 AMR

AF:

0.00204

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00403

Gnomad4 NFE

AF:

0.00455

Gnomad4 OTH

AF:

0.00124

Alfa

AF:

0.00585

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MUC12: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.1

CADD

Benign

5.3

DANN

Benign

0.11

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over