11-60061190-G-T

Variant names:

• chr11-60061190-G-T
• rs916530750
• NM_006138.5:c.30G>T

Variant summary

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

The NM_006138.5(MS4A3):​c.30G>T​(p.Glu10Asp) 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E10G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MS4A3 NM_006138.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.148
• Publications: 0 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: 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=0.07054755).

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.30G>T	p.Glu10Asp	missense	Exon 2 of 7	NP_006129.4
	MS4A3	NM_001031809.2		c.30G>T	p.Glu10Asp	missense	Exon 2 of 6	NP_001026979.1	Q96HJ5-2
	MS4A3	NM_001031666.2		c.-75-3072G>T		intron	N/A	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.30G>T	p.Glu10Asp	missense	Exon 2 of 7	ENSP00000278865.3	Q96HJ5-1
	MS4A3	ENST00000358152.6	TSL:5	c.30G>T	p.Glu10Asp	missense	Exon 2 of 6	ENSP00000350872.2	Q96HJ5-2
	MS4A3	ENST00000395032.6	TSL:2	c.-75-3072G>T		intron	N/A	ENSP00000378473.2	Q96HJ5-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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	0.10
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.3
DANN	Benign	0.63
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.15
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.65	N
REVEL	Benign	0.11
Sift	Benign	0.37	T
Sift4G	Benign	0.49	T
Polyphen		0.88	P
Vest4		0.17
MutPred		0.24		Loss of sheet (P = 0.1158)
MVP		0.088
MPC		0.018
ClinPred		0.38	T
GERP RS		-1.6
PromoterAI		0.018	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.080
gMVP		0.25
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs916530750; hg19: chr11-59828663;