Genetic Variant MS4A3:p.Val50Leu (chr11-60061308-G-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006138.5(MS4A3):c.148G>C(p.Val50Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000224 in 1,606,618 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

MS4A3
NM_006138.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.503

Publications

0 publications found

Variant links:

Genes affected

MS4A3 (HGNC:7317): (membrane spanning 4-domains A3) This gene encodes a member of the membrane-spanning 4A gene family. Members of this protein family are characterized by common structural features and similar intron/exon splice boundaries and display unique expression patterns among hematopoietic cells and nonlymphoid tissues. This family member likely plays a role in signal transduction and may function as a subunit associated with receptor complexes. The gene encoding this protein is localized to 11q12, among a cluster of related family members. Alternative splicing may result in multiple transcript variants; however, not all variants have been fully described. [provided by RefSeq, Jul 2008]

MS4A3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.024406374).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006138.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MS4A3	NM_006138.5	MANE Select	c.148G>C	p.Val50Leu	missense	Exon 2 of 7	NP_006129.4
MS4A3	NM_001031809.2		c.148G>C	p.Val50Leu	missense	Exon 2 of 6	NP_001026979.1	Q96HJ5-2
MS4A3	NM_001031666.2		c.-75-2954G>C		intron	N/A	NP_001026836.1	Q96HJ5-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MS4A3	ENST00000278865.8	TSL:1 MANE Select	c.148G>C	p.Val50Leu	missense	Exon 2 of 7	ENSP00000278865.3	Q96HJ5-1
MS4A3	ENST00000358152.6	TSL:5	c.148G>C	p.Val50Leu	missense	Exon 2 of 6	ENSP00000350872.2	Q96HJ5-2
MS4A3	ENST00000395032.6	TSL:2	c.-75-2954G>C		intron	N/A	ENSP00000378473.2	Q96HJ5-3

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

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

GnomAD2 exomes

AF:

0.0000496

AC:

AN:

242132

AF XY:

0.0000535

show subpopulations

Gnomad AFR exome

AF:

0.000747

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.0000103

AC:

AN:

1454304

Hom.:

Cov.:

AF XY:

0.00000968

AC XY:

AN XY:

723352

show subpopulations

African (AFR)

AF:

0.000455

AC:

AN:

32992

American (AMR)

AF:

0.00

AC:

AN:

42666

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25660

East Asian (EAS)

AF:

0.00

AC:

AN:

39554

South Asian (SAS)

AF:

0.00

AC:

AN:

84600

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53316

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5716

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109740

Other (OTH)

AF:

0.00

AC:

AN:

60060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

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

AF:

0.000138

AC:

AN:

152314

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.000505

AC:

AN:

41586

American (AMR)

AF:

0.00

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

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:

0.000130

Hom.:

Bravo

AF:

0.000121

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000741

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.59

CADD

Benign

4.3

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.093

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.48

M_CAP

Benign

0.0027

MetaRNN

Benign

0.024

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.8

PhyloP100

0.50

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.67

REVEL

Benign

0.016

Sift

Benign

0.090

Sift4G

Benign

0.23

Polyphen

0.048

Vest4

0.21

MVP

0.13

MPC

0.022

ClinPred

0.017

GERP RS

0.12

PromoterAI

0.032

Neutral

(source)

Varity_R

0.11

gMVP

0.23

Mutation Taster

=94/6

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

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