rs2304934

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/22 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: Uncertain_significance. The variant received 0 ACMG points.

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MS4A6E	NM_139249.4	MANE Select	c.28A>C	p.Thr10Pro	missense	Exon 2 of 5	NP_640342.1	Q96DS6
	MS4A6E	NR_170614.1		n.196A>C		non_coding_transcript_exon	Exon 2 of 6
	MS4A6E	NR_170615.1		n.196A>C		non_coding_transcript_exon	Exon 2 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MS4A6E	ENST00000684409.1	MANE Select	c.28A>C	p.Thr10Pro	missense	Exon 2 of 5	ENSP00000507799.1	Q96DS6
	MS4A6E	ENST00000300182.8	TSL:1	c.28A>C	p.Thr10Pro	missense	Exon 1 of 4	ENSP00000300182.4	Q96DS6
	MS4A6E	ENST00000969922.1		c.28A>C	p.Thr10Pro	missense	Exon 3 of 6	ENSP00000639981.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
PhyloP100		-0.11
PromoterAI		-0.015	Neutral
Varity_R		0.27
gMVP		0.45
Mutation Taster		=96/4	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2304934; hg19: chr11-60102396;