rs2304934

Positions:

• chr11-60334923-A-C
• chr11-60334923-A-G
• chr11-60334923-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_139249.4(MS4A6E):​c.28A>C​(p.Thr10Pro) 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. 13/21 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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10827294).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MS4A6E	NM_139249.4	c.28A>C	p.Thr10Pro	missense_variant	2/5	ENST00000684409.1
MS4A6E	NR_170614.1	n.196A>C		non_coding_transcript_exon_variant	2/6
MS4A6E	NR_170615.1	n.196A>C		non_coding_transcript_exon_variant	2/5
MS4A6E	NR_170616.1	n.196A>C		non_coding_transcript_exon_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MS4A6E	ENST00000684409.1	c.28A>C	p.Thr10Pro	missense_variant	2/5		NM_139249.4	P1
MS4A6E	ENST00000300182.8	c.28A>C	p.Thr10Pro	missense_variant	1/4	1		P1
MS4A6E	ENST00000532756.1			upstream_gene_variant		4

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	0.11
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	8.3
DANN	Benign	0.94
DEOGEN2	Benign	0.040	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0079	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.037
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.011	D
Polyphen		0.96	P
Vest4		0.26
MutPred		0.28		Loss of sheet (P = 0.0181);
MVP		0.043
MPC		0.16
ClinPred		0.68	D
GERP RS		-2.8
Varity_R		0.27
gMVP		0.45

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;