rs201491900

Variant names:

• chr11-60462424-T-A
• NM_152866.3:c.50T>A

Your query was ambiguous. Multiple possible variants found:

• chr11-60462424-T-A
• chr11-60462424-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152866.3(MS4A1):​c.50T>A​(p.Met17Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M17T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MS4A1 NM_152866.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980

Genes affected

MS4A1 (HGNC:7315): (membrane spanning 4-domains A1) This gene encodes a member of the membrane-spanning 4A gene family. Members of this nascent 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 gene encodes a B-lymphocyte surface molecule which plays a role in the development and differentiation of B-cells into plasma cells. This family member is localized to 11q12, among a cluster of family members. Alternative splicing of this gene results in two transcript variants which encode the same protein. [provided by RefSeq, Jul 2008]

ACMG classification

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=0.034953).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MS4A1	NM_152866.3	c.50T>A	p.Met17Lys	missense_variant	Exon 3 of 8	ENST00000345732.9	NP_690605.1
MS4A1	NM_021950.4	c.50T>A	p.Met17Lys	missense_variant	Exon 2 of 7		NP_068769.2
MS4A1	NM_152867.2	c.50T>A	p.Met17Lys	missense_variant	Exon 2 of 7		NP_690606.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MS4A1	ENST00000345732.9	c.50T>A	p.Met17Lys	missense_variant	Exon 3 of 8	1	NM_152866.3	ENSP00000314620.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461888 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.3
DANN	Benign	0.81
DEOGEN2	Benign	0.10	T;T;T;.;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.58	.;T;.;T;T;T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.035	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;.;L;L;.;L
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.77	N;N;N;N;N;N
REVEL	Benign	0.024
Sift	Benign	0.42	T;T;T;D;D;T
Sift4G	Uncertain	0.038	D;D;D;T;T;D
Polyphen		0.042	B;B;B;.;.;B
Vest4		0.35
MutPred		0.28		Gain of ubiquitination at M17 (P = 0.0031);Gain of ubiquitination at M17 (P = 0.0031);Gain of ubiquitination at M17 (P = 0.0031);Gain of ubiquitination at M17 (P = 0.0031);.;Gain of ubiquitination at M17 (P = 0.0031);
MVP		0.088
MPC		0.051
ClinPred		0.068	T
GERP RS		-3.6
Varity_R		0.16
gMVP		0.45

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-60229897;