11-60334923-A-T

Variant names:

• chr11-60334923-A-T
• rs2304934
• NM_139249.4:c.28A>T

Variant summary

Our verdict is Likely benign. The variant received -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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MS4A6E NM_139249.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.111
• Publications: 26 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139249.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MS4A6E	NM_139249.4	MANE Select	c.28A>T	p.Thr10Ser	missense	Exon 2 of 5	NP_640342.1
	MS4A6E	NR_170614.1		n.196A>T		non_coding_transcript_exon	Exon 2 of 6
	MS4A6E	NR_170615.1		n.196A>T		non_coding_transcript_exon	Exon 2 of 5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MS4A6E	ENST00000684409.1	MANE Select	c.28A>T	p.Thr10Ser	missense	Exon 2 of 5	ENSP00000507799.1
	MS4A6E	ENST00000300182.8	TSL:1	c.28A>T	p.Thr10Ser	missense	Exon 1 of 4	ENSP00000300182.4
	MS4A6E	ENST00000530509.1	TSL:3	n.-54A>T		upstream_gene	N/A	ENSP00000436675.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 18981

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		-0.11
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
PromoterAI		-0.0035	Neutral
Varity_R		0.058
gMVP		0.19
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs2304934; hg19: chr11-60102396;