chr11-60334954-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_139249.4(MS4A6E):ā€‹c.59A>Gā€‹(p.Asn20Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000713 in 1,614,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000079 ( 0 hom., cov: 32)
Exomes š‘“: 0.000070 ( 0 hom. )

Consequence

MS4A6E
NM_139249.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.17
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.008702785).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MS4A6ENM_139249.4 linkuse as main transcriptc.59A>G p.Asn20Ser missense_variant 2/5 ENST00000684409.1
MS4A6ENR_170614.1 linkuse as main transcriptn.227A>G non_coding_transcript_exon_variant 2/6
MS4A6ENR_170615.1 linkuse as main transcriptn.227A>G non_coding_transcript_exon_variant 2/5
MS4A6ENR_170616.1 linkuse as main transcriptn.227A>G non_coding_transcript_exon_variant 2/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MS4A6EENST00000684409.1 linkuse as main transcriptc.59A>G p.Asn20Ser missense_variant 2/5 NM_139249.4 P1
MS4A6EENST00000300182.8 linkuse as main transcriptc.59A>G p.Asn20Ser missense_variant 1/41 P1
MS4A6EENST00000530509.1 linkuse as main transcript upstream_gene_variant 3
MS4A6EENST00000532756.1 linkuse as main transcript upstream_gene_variant 4

Frequencies

GnomAD3 genomes
AF:
0.0000789
AC:
12
AN:
152170
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00768
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000716
AC:
18
AN:
251476
Hom.:
0
AF XY:
0.0000956
AC XY:
13
AN XY:
135916
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000123
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000705
AC:
103
AN:
1461862
Hom.:
0
Cov.:
37
AF XY:
0.0000701
AC XY:
51
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000818
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.0000789
AC:
12
AN:
152170
Hom.:
0
Cov.:
32
AF XY:
0.0000942
AC XY:
7
AN XY:
74334
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000823
Hom.:
0
Bravo
AF:
0.0000793
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000906
AC:
11
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000178

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 02, 2022The c.59A>G (p.N20S) alteration is located in exon 1 (coding exon 1) of the MS4A6E gene. This alteration results from a A to G substitution at nucleotide position 59, causing the asparagine (N) at amino acid position 20 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.068
BayesDel_addAF
Benign
-0.64
T
BayesDel_noAF
Benign
-0.93
CADD
Benign
0.019
DANN
Benign
0.43
DEOGEN2
Benign
0.0020
T
Eigen
Benign
-1.8
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.0017
N
LIST_S2
Benign
0.64
T
M_CAP
Benign
0.0043
T
MetaRNN
Benign
0.0087
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.11
N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-1.4
N
REVEL
Benign
0.011
Sift
Benign
0.44
T
Sift4G
Benign
0.57
T
Polyphen
0.0040
B
Vest4
0.065
MVP
0.043
MPC
0.029
ClinPred
0.037
T
GERP RS
-4.8
Varity_R
0.024
gMVP
0.13

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.

Other links and lift over

dbSNP: rs371238053; hg19: chr11-60102427; API