rs528823

chr11-60069624-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_006138.5(MS4A3):c.564C>T(p.Thr188=) 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

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

Verdict is Benign. Variant got -8 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MS4A3	NM_006138.5	c.564C>T	p.Thr188=	synonymous_variant	6/7	ENST00000278865.8
MS4A3	NM_001031809.2	c.426C>T	p.Thr142=	synonymous_variant	5/6
MS4A3	NM_001031666.2	c.195C>T	p.Thr65=	synonymous_variant	4/5
MS4A3	XM_011545363.4	c.384C>T	p.Thr128=	synonymous_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MS4A3	ENST00000278865.8	c.564C>T	p.Thr188=	synonymous_variant	6/7	1	NM_006138.5	P1

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

GnomAD3 exomes AF: 0.281 AC: 70477 AN: 250936 Hom.: 11046 AF XY: 0.297 AC XY: 40219 AN XY: 135600

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 SAS exome AF: 0.486

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

Gnomad4 AFR exome AF: 0.262

Gnomad4 AMR exome AF: 0.177

Gnomad4 ASJ exome AF: 0.276

Gnomad4 EAS exome AF: 0.189

Gnomad4 SAS exome AF: 0.487

Gnomad4 FIN exome AF: 0.215

Gnomad4 NFE exome AF: 0.284

Gnomad4 OTH exome AF: 0.291

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

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.489

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.292

Alfa AF: 0.286 Hom.: 15057

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.53
Dann	Benign	0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

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