Variant 11-60501118-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000016913.8(MS4A12):c.350G>A(p.Arg117Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MS4A12
ENST00000016913.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -6.30

Variant links:

Genes affected

MS4A12 (HGNC:13370): (membrane spanning 4-domains A12) The protein encoded by this gene is a cell surface protein found primarily in the apical membrane of colonocytes. Silencing of this gene in colon cancer cells inhibits the proliferation, cell motility, and chemotactic invasion of cells. This gene is part of a cluster of similar genes found on chromosome 11. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2009]

MS4A12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0587292).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MS4A12	NM_017716.3 linkuse as main transcript	c.350G>A	p.Arg117Lys	missense_variant	3/7	ENST00000016913.8	NP_060186.2	Q9NXJ0-1
MS4A12	XM_011545117.3 linkuse as main transcript	c.350G>A	p.Arg117Lys	missense_variant	4/8		XP_011543419.1	Q9NXJ0-1
MS4A12	NM_001164470.2 linkuse as main transcript	c.277-865G>A		intron_variant			NP_001157942.1	Q9NXJ0-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MS4A12	ENST00000016913.8 linkuse as main transcript	c.350G>A	p.Arg117Lys	missense_variant	3/7	1	NM_017716.3	ENSP00000016913.4	Q9NXJ0-1
MS4A12	ENST00000537076.5 linkuse as main transcript	c.277-865G>A		intron_variant		5		ENSP00000440424.1	Q9NXJ0-2
MS4A12	ENST00000526784.5 linkuse as main transcript	c.277-865G>A		intron_variant		3		ENSP00000431959.1	E9PIX5
MS4A12	ENST00000530007.1 linkuse as main transcript	c.*7G>A		downstream_gene_variant		3		ENSP00000434783.1	E9PNI3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

250870

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135606

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461428

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727028

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 22, 2023

The c.350G>A (p.R117K) alteration is located in exon 3 (coding exon 2) of the MS4A12 gene. This alteration results from a G to A substitution at nucleotide position 350, causing the arginine (R) at amino acid position 117 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.0010

DANN

Benign

0.31

DEOGEN2

Benign

0.0015

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.4

FATHMM_MKL

Benign

0.00099

LIST_S2

Benign

0.13

M_CAP

Benign

0.0028

MetaRNN

Benign

0.059

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.090

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.070

REVEL

Benign

0.033

Sift

Benign

0.94

Sift4G

Benign

0.91

Polyphen

0.0

Vest4

0.17

MutPred

0.54

Gain of methylation at R117 (P = 0.0163);

MVP

0.030

MPC

0.039

ClinPred

0.028

GERP RS

-7.0

Varity_R

0.036

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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