11-60334923-A-G

Position:

• chr11-60334923-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139249.4(MS4A6E):​c.28A>G​(p.Thr10Ala) 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 1,610,398 control chromosomes in the GnomAD database, including 89,867 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 (8424 hom., cov: 32)
  • Exomes 𝑓: 0.33 (81443 hom.)
• 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]

MS4A6E (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.1028645E-5).
• 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	c.28A>G	p.Thr10Ala	missense_variant	2/5	ENST00000684409.1	NP_640342.1
MS4A6E	NR_170614.1	n.196A>G		non_coding_transcript_exon_variant	2/6
MS4A6E	NR_170615.1	n.196A>G		non_coding_transcript_exon_variant	2/5
MS4A6E	NR_170616.1	n.196A>G		non_coding_transcript_exon_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MS4A6E	ENST00000684409.1	c.28A>G	p.Thr10Ala	missense_variant	2/5		NM_139249.4	ENSP00000507799.1
MS4A6E	ENST00000300182.8	c.28A>G	p.Thr10Ala	missense_variant	1/4	1		ENSP00000300182.4
MS4A6E	ENST00000532756.1	n.-48A>G		upstream_gene_variant		4		ENSP00000432963.1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48581 AN: 151924 Hom.: 8402 Cov.: 32

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.292

GnomAD3 exomes AF: 0.324 AC: 81533 AN: 251450 Hom.: 14803 AF XY: 0.315 AC XY: 42789 AN XY: 135904

Gnomad AFR exome AF: 0.250

Gnomad AMR exome AF: 0.385

Gnomad ASJ exome AF: 0.247

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: 0.326 AC: 475808 AN: 1458356 Hom.: 81443 Cov.: 37 AF XY: 0.321 AC XY: 232709 AN XY: 725756

Gnomad4 AFR exome AF: 0.249

Gnomad4 AMR exome AF: 0.378

Gnomad4 ASJ exome AF: 0.252

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: 0.320 AC: 48646 AN: 152042 Hom.: 8424 Cov.: 32 AF XY: 0.328 AC XY: 24364 AN XY: 74308

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.265

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.571

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.295

Alfa AF: 0.319 Hom.: 6055

Bravo AF: 0.304

TwinsUK AF: 0.343 AC: 1272

ALSPAC AF: 0.328 AC: 1264

ESP6500AA AF: 0.260 AC: 1144

ESP6500EA AF: 0.336 AC: 2888

ExAC AF: 0.318 AC: 38654

Asia WGS AF: 0.223 AC: 775 AN: 3478

EpiCase AF: 0.302

EpiControl AF: 0.302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.99
DANN	Benign	0.96
DEOGEN2	Benign	0.037	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0044	N
LIST_S2	Benign	0.56	T
MetaRNN	Benign	0.000051	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.6	L
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.022
Sift	Benign	0.086	T
Sift4G	Uncertain	0.023	D
Polyphen		0.11	B
Vest4		0.0080
MPC		0.052
ClinPred		0.010	T
GERP RS		-2.8
Varity_R		0.051
gMVP		0.24

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; COSMIC: COSV55726789; COSMIC: COSV55726789;