rs528823

Variant names:

• chr11-60069624-C-T
• rs528823
• NM_006138.5:c.564C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_006138.5(MS4A3):​c.564C>T​(p.Thr188Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 1,610,468 control chromosomes in the GnomAD database, including 69,586 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 (5848 hom., cov: 32)
  • Exomes 𝑓: 0.29 (63738 hom.)
• Consequence: MS4A3 NM_006138.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.239
• Publications: 28 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MS4A3	NM_006138.5	MANE Select	c.564C>T	p.Thr188Thr	synonymous	Exon 6 of 7	NP_006129.4
	MS4A3	NM_001031809.2		c.426C>T	p.Thr142Thr	synonymous	Exon 5 of 6	NP_001026979.1	Q96HJ5-2
	MS4A3	NM_001031666.2		c.195C>T	p.Thr65Thr	synonymous	Exon 4 of 5	NP_001026836.1	Q96HJ5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MS4A3	ENST00000278865.8	TSL:1 MANE Select	c.564C>T	p.Thr188Thr	synonymous	Exon 6 of 7	ENSP00000278865.3	Q96HJ5-1
	MS4A3	ENST00000358152.6	TSL:5	c.426C>T	p.Thr142Thr	synonymous	Exon 5 of 6	ENSP00000350872.2	Q96HJ5-2
	MS4A3	ENST00000395032.6	TSL:2	c.195C>T	p.Thr65Thr	synonymous	Exon 4 of 5	ENSP00000378473.2	Q96HJ5-3

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41379 AN: 151890 Hom.: 5847 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.288

GnomAD2 exomes AF: 0.281 AC: 70477 AN: 250936 AF XY: 0.297

Gnomad AFR exome AF: 0.262

Gnomad AMR exome AF: 0.169

Gnomad ASJ exome AF: 0.270

Gnomad EAS exome AF: 0.214

Gnomad FIN exome AF: 0.214

Gnomad NFE exome AF: 0.287

Gnomad OTH exome AF: 0.272

GnomAD4 exome AF: 0.288 AC: 419586 AN: 1458460 Hom.: 63738 Cov.: 32 AF XY: 0.295 AC XY: 213919 AN XY: 725596

African (AFR) AF: 0.262 AC: 8736 AN: 33394

American (AMR) AF: 0.177 AC: 7883 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 7215 AN: 26096

East Asian (EAS) AF: 0.189 AC: 7491 AN: 39616

South Asian (SAS) AF: 0.487 AC: 41840 AN: 85972

European-Finnish (FIN) AF: 0.215 AC: 11500 AN: 53384

Middle Eastern (MID) AF: 0.365 AC: 2101 AN: 5756

European-Non Finnish (NFE) AF: 0.284 AC: 315283 AN: 1109346

Other (OTH) AF: 0.291 AC: 17537 AN: 60250

GnomAD4 genome AF: 0.272 AC: 41407 AN: 152008 Hom.: 5848 Cov.: 32 AF XY: 0.273 AC XY: 20318 AN XY: 74312

African (AFR) AF: 0.268 AC: 11098 AN: 41440

American (AMR) AF: 0.229 AC: 3491 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 890 AN: 3470

East Asian (EAS) AF: 0.220 AC: 1135 AN: 5166

South Asian (SAS) AF: 0.489 AC: 2354 AN: 4818

European-Finnish (FIN) AF: 0.202 AC: 2139 AN: 10564

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19349 AN: 67964

Other (OTH) AF: 0.292 AC: 615 AN: 2108

Alfa AF: 0.283 Hom.: 21475

Bravo AF: 0.269

Asia WGS AF: 0.352 AC: 1224 AN: 3478

EpiCase AF: 0.301

EpiControl AF: 0.300

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.53
DANN	Benign	0.47
PhyloP100		0.24
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.21		Position offset: -50

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs528823; hg19: chr11-59837097; COSMIC: COSV53936247;