Genetic Variant MS4A3:c.*915T>G (chr11-60071148-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006138.5(MS4A3):c.*915T>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,136 control chromosomes in the GnomAD database, including 5,897 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.27 ( 5894 hom., cov: 32)

Exomes 𝑓: 0.16 ( 3 hom. )

Consequence

MS4A3
NM_006138.5 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.676

Publications

16 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
MS4A3	NM_006138.5 link	c.*915T>G	downstream_gene_variant	ENST00000278865.8	NP_006129.4	Q96HJ5-1
MS4A3	NM_001031809.2 link	c.*915T>G	downstream_gene_variant		NP_001026979.1	Q96HJ5-2
MS4A3	NM_001031666.2 link	c.*915T>G	downstream_gene_variant		NP_001026836.1	Q96HJ5-3
MS4A3	XM_011545363.4 link	c.*915T>G	downstream_gene_variant		XP_011543665.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
MS4A3	ENST00000278865.8 link	c.*915T>G	downstream_gene_variant	1	NM_006138.5	ENSP00000278865.3	Q96HJ5-1
MS4A3	ENST00000358152.6 link	c.*915T>G	downstream_gene_variant	5		ENSP00000350872.2	Q96HJ5-2
MS4A3	ENST00000528952.1 link	n.*167T>G	downstream_gene_variant	2

Frequencies

GnomAD3 genomes

AF:

0.273

AC:

41533

AN:

151890

Hom.:

5893

Cov.:

show subpopulations

Gnomad AFR

AF:

0.269

Gnomad AMI

AF:

0.255

Gnomad AMR

AF:

0.230

Gnomad ASJ

AF:

0.256

Gnomad EAS

AF:

0.221

Gnomad SAS

AF:

0.494

Gnomad FIN

AF:

0.202

Gnomad MID

AF:

0.350

Gnomad NFE

AF:

0.285

Gnomad OTH

AF:

0.287

GnomAD4 exome

AF:

0.156

AC:

AN:

128

Hom.:

Cov.:

AF XY:

0.204

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.164

AC:

AN:

122

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.561

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.273

AC:

41561

AN:

152008

Hom.:

5894

Cov.:

AF XY:

0.274

AC XY:

20385

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.269

AC:

11162

AN:

41438

American (AMR)

AF:

0.229

AC:

3502

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.256

AC:

890

AN:

3470

East Asian (EAS)

AF:

0.220

AC:

1139

AN:

5172

South Asian (SAS)

AF:

0.494

AC:

2380

AN:

4816

European-Finnish (FIN)

AF:

0.202

AC:

2138

AN:

10570

Middle Eastern (MID)

AF:

0.353

AC:

103

AN:

292

European-Non Finnish (NFE)

AF:

0.286

AC:

19400

AN:

67948

Other (OTH)

AF:

0.291

AC:

614

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1547

3094

4640

6187

7734

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

444

888

1332

1776

2220

<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:

0.291

Hom.:

4584

Bravo

AF:

0.269

Asia WGS

AF:

0.355

AC:

1233

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

2.6

(source)

DANN

Benign

0.47

PhyloP100

0.68

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over