11-60703439-T-G

Position:

• chr11-60703439-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_031457.2(MS4A8):​c.281T>G​(p.Leu94Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/21 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)
• Consequence: MS4A8 NM_031457.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.355

Genes affected

MS4A8 (HGNC:13380): (membrane spanning 4-domains A8) 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. The gene encoding this protein is localized to 11q12.3, among a cluster of family members. [provided by RefSeq, Jul 2008]

MS4A8 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MS4A8	NM_031457.2	c.281T>G	p.Leu94Arg	missense_variant	3/7	ENST00000300226.7	NP_113645.1
LOC105369321	XR_001748240.2	n.191+300A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MS4A8	ENST00000300226.7	c.281T>G	p.Leu94Arg	missense_variant	3/7	1	NM_031457.2	ENSP00000300226.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.281T>G (p.L94R) alteration is located in exon 3 (coding exon 2) of the MS4A8 gene. This alteration results from a T to G substitution at nucleotide position 281, causing the leucine (L) at amino acid position 94 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	14
DANN	Benign	0.52
DEOGEN2	Benign	0.030	T;.
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.37	T;T
M_CAP	Benign	0.0043	T
MetaRNN	Uncertain	0.51	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.24
Sift	Benign	0.59	T;T
Sift4G	Benign	0.32	T;T
Polyphen		0.29	B;B
Vest4		0.58
MutPred		0.81		Gain of methylation at L94 (P = 0.0292);Gain of methylation at L94 (P = 0.0292);
MVP		0.12
MPC		0.54
ClinPred		0.13	T
GERP RS		1.1
Varity_R		0.18
gMVP		0.29

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-60470912;