11-60334923-A-T

Position:

• chr11-60334923-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_139249.4(MS4A6E):​c.28A>T​(p.Thr10Ser) 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. 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. T10A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MS4A6E NM_139249.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.111

Genes affected

MS4A6E (HGNC:14285): (membrane spanning 4-domains A6E) This gene encodes a member of the membrane-spanning 4A gene family. Members of this nascent 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]

MS4A6E (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05310744).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MS4A6E	NM_139249.4	c.28A>T	p.Thr10Ser	missense_variant	2/5	ENST00000684409.1	NP_640342.1
MS4A6E	NR_170614.1	n.196A>T		non_coding_transcript_exon_variant	2/6
MS4A6E	NR_170615.1	n.196A>T		non_coding_transcript_exon_variant	2/5
MS4A6E	NR_170616.1	n.196A>T		non_coding_transcript_exon_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MS4A6E	ENST00000684409.1	c.28A>T	p.Thr10Ser	missense_variant	2/5		NM_139249.4	ENSP00000507799.1
MS4A6E	ENST00000300182.8	c.28A>T	p.Thr10Ser	missense_variant	1/4	1		ENSP00000300182.4
MS4A6E	ENST00000532756.1	n.-48A>T		upstream_gene_variant		4		ENSP00000432963.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.63
DANN	Benign	0.94
DEOGEN2	Benign	0.0057	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0051	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.015
Sift	Uncertain	0.024	D
Sift4G	Benign	0.15	T
Polyphen		0.11	B
Vest4		0.057
MutPred		0.23		Loss of sheet (P = 0.0315);
MVP		0.043
MPC		0.045
ClinPred		0.062	T
GERP RS		-2.8
Varity_R		0.058
gMVP		0.19

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

LitVar

Other links and lift over

dbSNP: rs2304934; hg19: chr11-60102396;