chr11-60297290-G-C

Variant names:

• chr11-60297290-G-C
• rs377643559
• NM_148975.3:c.295G>C

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.295G>C​(p.Val99Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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. V99M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MS4A4A NM_148975.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.156
• Publications: 7 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=0.16806939).

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.295G>C	p.Val99Leu	missense	Exon 3 of 7	NP_683876.1	Q96JQ5-1
	MS4A4A	NM_024021.4		c.238G>C	p.Val80Leu	missense	Exon 4 of 8	NP_076926.2
	MS4A4A	NM_001243266.2		c.295G>C	p.Val99Leu	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.295G>C	p.Val99Leu	missense	Exon 3 of 7	ENSP00000338648.4	Q96JQ5-1
	MS4A4A	ENST00000649552.2		c.313G>C	p.Val105Leu	missense	Exon 4 of 8	ENSP00000497952.2	A0A3B3ITV6
	MS4A4A	ENST00000679553.1		c.313G>C	p.Val105Leu	missense	Exon 3 of 7	ENSP00000505712.1	A0A7P0T9I4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	9.2
DANN	Benign	0.78
DEOGEN2	Benign	0.0063	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.91	L
PhyloP100		0.16
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.090
Sift	Benign	0.28	T
Sift4G	Benign	0.28	T
Polyphen		0.91	P
Vest4		0.26
MutPred		0.50		Gain of glycosylation at S98 (P = 0.1401)
MVP		0.055
MPC		0.19
ClinPred		0.66	D
GERP RS		-0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.20
gMVP		0.10
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs377643559; hg19: chr11-60064763;