NM_148975.3:c.268A>G

Variant names:

• chr11-60297263-A-G
• rs1313190576
• NM_148975.3:c.268A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_148975.3(MS4A4A):​c.268A>G​(p.Asn90Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000185 in 1,461,394 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: MS4A4A NM_148975.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.699
• Publications: 0 publications found

Genes affected

MS4A4A (HGNC:13371): (membrane spanning 4-domains A4A) This gene encodes a member of the membrane-spanning 4A gene family. Members of this nascent protein family are characterized by common structural features, similar intron/exon splice boundaries, and display unique expression patterns in hematopoietic cells and nonlymphoid tissues. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.091391146).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_148975.3. 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
	MS4A4A	NM_148975.3	MANE Select	c.268A>G	p.Asn90Asp	missense	Exon 3 of 7	NP_683876.1	Q96JQ5-1
	MS4A4A	NM_024021.4		c.211A>G	p.Asn71Asp	missense	Exon 4 of 8	NP_076926.2
	MS4A4A	NM_001243266.2		c.268A>G	p.Asn90Asp	missense	Exon 3 of 6	NP_001230195.1	Q96JQ5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MS4A4A	ENST00000337908.5	TSL:1 MANE Select	c.268A>G	p.Asn90Asp	missense	Exon 3 of 7	ENSP00000338648.4	Q96JQ5-1
	MS4A4A	ENST00000649552.2		c.286A>G	p.Asn96Asp	missense	Exon 4 of 8	ENSP00000497952.2	A0A3B3ITV6
	MS4A4A	ENST00000679553.1		c.286A>G	p.Asn96Asp	missense	Exon 3 of 7	ENSP00000505712.1	A0A7P0T9I4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251170 AF XY: 0.00

Gnomad AFR exome AF: 0.00

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: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000185 AC: 27 AN: 1461394 Hom.: 0 Cov.: 30 AF XY: 0.0000179 AC XY: 13 AN XY: 726992

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000243 AC: 27 AN: 1111646

Other (OTH) AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.41
DANN	Benign	0.43
DEOGEN2	Benign	0.0038	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0068	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.65	N
PhyloP100		-0.70
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.16
Sift	Benign	0.62	T
Sift4G	Benign	0.59	T
Polyphen		0.0040	B
Vest4		0.12
MutPred		0.40		Loss of sheet (P = 0.0817)
MVP		0.030
MPC		0.087
ClinPred		0.039	T
GERP RS		-3.6
Varity_R		0.061
gMVP		0.038
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1313190576; hg19: chr11-60064736;