Variant 11-60335034-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_139249.4(MS4A6E):c.139G>T(p.Val47Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 1,613,452 control chromosomes in the GnomAD database, including 89,900 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.32 ( 8395 hom., cov: 31)

Exomes 𝑓: 0.33 ( 81505 hom. )

Consequence

MS4A6E
NM_139249.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.164

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:

MS4A6E (HGNC:):

MS4A6E links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.3646483E-4).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MS4A6E	NM_139249.4 linkuse as main transcript	c.139G>T	p.Val47Phe	missense_variant	2/5	ENST00000684409.1	NP_640342.1	Q96DS6
MS4A6E	NR_170614.1 linkuse as main transcript	n.307G>T		non_coding_transcript_exon_variant	2/6
MS4A6E	NR_170615.1 linkuse as main transcript	n.307G>T		non_coding_transcript_exon_variant	2/5
MS4A6E	NR_170616.1 linkuse as main transcript	n.307G>T		non_coding_transcript_exon_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MS4A6E	ENST00000684409.1 linkuse as main transcript	c.139G>T	p.Val47Phe	missense_variant	2/5		NM_139249.4	ENSP00000507799.1	Q96DS6
MS4A6E	ENST00000300182.8 linkuse as main transcript	c.139G>T	p.Val47Phe	missense_variant	1/4	1		ENSP00000300182.4	Q96DS6
MS4A6E	ENST00000530509.1 linkuse as main transcript	n.58G>T		non_coding_transcript_exon_variant	1/4	3		ENSP00000436675.1	H0YEW2
MS4A6E	ENST00000532756.1 linkuse as main transcript	n.64G>T		non_coding_transcript_exon_variant	1/5	4		ENSP00000432963.1	H0YD45

Frequencies

GnomAD3 genomes

AF:

0.319

AC:

48458

AN:

151798

Hom.:

8373

Cov.:

show subpopulations

Gnomad AFR

AF:

0.250

Gnomad AMI

AF:

0.287

Gnomad AMR

AF:

0.361

Gnomad ASJ

AF:

0.269

Gnomad EAS

AF:

0.264

Gnomad SAS

AF:

0.148

Gnomad FIN

AF:

0.570

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.334

Gnomad OTH

AF:

0.292

GnomAD3 exomes

AF:

0.324

AC:

81431

AN:

251242

Hom.:

14775

AF XY:

0.315

AC XY:

42737

AN XY:

135794

show subpopulations

Gnomad AFR exome

AF:

0.249

Gnomad AMR exome

AF:

0.385

Gnomad ASJ exome

AF:

0.248

Gnomad EAS exome

AF:

0.269

Gnomad SAS exome

AF:

0.144

Gnomad FIN exome

AF:

0.559

Gnomad NFE exome

AF:

0.337

Gnomad OTH exome

AF:

0.306

GnomAD4 exome

AF:

0.327

AC:

477543

AN:

1461536

Hom.:

81505

Cov.:

AF XY:

0.321

AC XY:

233442

AN XY:

727070

show subpopulations

Gnomad4 AFR exome

AF:

0.248

Gnomad4 AMR exome

AF:

0.377

Gnomad4 ASJ exome

AF:

0.253

Gnomad4 EAS exome

AF:

0.298

Gnomad4 SAS exome

AF:

0.149

Gnomad4 FIN exome

AF:

0.544

Gnomad4 NFE exome

AF:

0.335

Gnomad4 OTH exome

AF:

0.303

GnomAD4 genome

AF:

0.319

AC:

48523

AN:

151916

Hom.:

8395

Cov.:

AF XY:

0.327

AC XY:

24295

AN XY:

74238

show subpopulations

Gnomad4 AFR

AF:

0.250

Gnomad4 AMR

AF:

0.362

Gnomad4 ASJ

AF:

0.269

Gnomad4 EAS

AF:

0.264

Gnomad4 SAS

AF:

0.150

Gnomad4 FIN

AF:

0.570

Gnomad4 NFE

AF:

0.334

Gnomad4 OTH

AF:

0.295

Alfa

AF:

0.310

Hom.:

18716

Bravo

AF:

0.304

TwinsUK

AF:

0.345

AC:

1281

ALSPAC

AF:

0.330

AC:

1273

ESP6500AA

AF:

0.258

AC:

1137

ESP6500EA

AF:

0.336

AC:

2890

ExAC

AF:

0.318

AC:

38662

Asia WGS

AF:

0.223

AC:

776

AN:

3478

EpiCase

AF:

0.302

EpiControl

AF:

0.303

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

8.4

DANN

Benign

0.96

DEOGEN2

Benign

0.13

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.60

MetaRNN

Benign

0.00014

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.69

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.044

Sift

Benign

0.044

Sift4G

Benign

0.098

Polyphen

1.0

Vest4

0.11

MPC

0.039

ClinPred

0.035

GERP RS

2.2

Varity_R

0.14

gMVP

0.54

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

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