dbSNP rs1227810109: MS4A6E:p.Asp109Asn (chr11-60337918-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_139249.4(MS4A6E):c.325G>A(p.Asp109Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. D109H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

MS4A6E
NM_139249.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.130

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.22844782).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MS4A6E	NM_139249.4 link	c.325G>A	p.Asp109Asn	missense_variant	Exon 3 of 5	ENST00000684409.1	NP_640342.1	Q96DS6
MS4A6E	NR_170614.1 link	n.493G>A		non_coding_transcript_exon_variant	Exon 3 of 6
MS4A6E	NR_170616.1 link	n.613G>A		non_coding_transcript_exon_variant	Exon 4 of 6
MS4A6E	NR_170615.1 link	n.541+72G>A		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MS4A6E	ENST00000684409.1 link	c.325G>A	p.Asp109Asn	missense_variant	Exon 3 of 5		NM_139249.4	ENSP00000507799.1	Q96DS6
MS4A6E	ENST00000300182.8 link	c.325G>A	p.Asp109Asn	missense_variant	Exon 2 of 4	1		ENSP00000300182.4	Q96DS6
MS4A6E	ENST00000532756.1 link	n.250G>A		non_coding_transcript_exon_variant	Exon 2 of 5	4		ENSP00000432963.1	H0YD45
MS4A6E	ENST00000530509.1 link	n.*112+72G>A		intron_variant	Intron 3 of 3	3		ENSP00000436675.1	H0YEW2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251226

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135754

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.8

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0022

Eigen

Benign

-0.95

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.69

M_CAP

Benign

0.0047

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.2

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.8

REVEL

Benign

0.060

Sift

Benign

0.19

Sift4G

Benign

0.43

Polyphen

0.20

Vest4

0.039

MutPred

0.66

Loss of loop (P = 0.0203);

MVP

0.068

MPC

0.065

ClinPred

0.25

GERP RS

0.91

Varity_R

0.065

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over