11-60706994-A-G

Position:

• chr11-60706994-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000300226.7(MS4A8):​c.349A>G​(p.Ile117Val) 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. 14/21 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 ENST00000300226.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.411

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30153024).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MS4A8	NM_031457.2	c.349A>G	p.Ile117Val	missense_variant	4/7	ENST00000300226.7	NP_113645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MS4A8	ENST00000300226.7	c.349A>G	p.Ile117Val	missense_variant	4/7	1	NM_031457.2	ENSP00000300226	P1

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

Sep 30, 2021

The c.349A>G (p.I117V) alteration is located in exon 4 (coding exon 3) of the MS4A8 gene. This alteration results from a A to G substitution at nucleotide position 349, causing the isoleucine (I) at amino acid position 117 to be replaced by a valine (V). 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	Benign	0.10
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	11
DANN	Uncertain	0.99
DEOGEN2	Benign	0.037	T;.
Eigen	Benign	-0.092
Eigen_PC	Benign	-0.023
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.58	T;T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.8	L;.
MutationTaster	Benign	0.97	D
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.57	N;N
REVEL	Benign	0.14
Sift	Benign	0.12	T;T
Sift4G	Benign	0.14	T;T
Polyphen		0.77	P;B
Vest4		0.20
MutPred		0.78		Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP		0.18
MPC		0.30
ClinPred		0.28	T
GERP RS		4.4
Varity_R		0.097
gMVP		0.28

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: chr11-60474467;