chr11-60334935-C-T

Variant summary

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

The NM_139249.4(MS4A6E):​c.40C>T​(p.Leu14Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000496 in 1,614,094 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

MS4A6E
NM_139249.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0830
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=0.053035527).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MS4A6ENM_139249.4 linkuse as main transcriptc.40C>T p.Leu14Phe missense_variant 2/5 ENST00000684409.1
MS4A6ENR_170614.1 linkuse as main transcriptn.208C>T non_coding_transcript_exon_variant 2/6
MS4A6ENR_170615.1 linkuse as main transcriptn.208C>T non_coding_transcript_exon_variant 2/5
MS4A6ENR_170616.1 linkuse as main transcriptn.208C>T 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.40C>T p.Leu14Phe missense_variant 2/5 NM_139249.4 P1
MS4A6EENST00000300182.8 linkuse as main transcriptc.40C>T p.Leu14Phe 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:
0.000210
AC:
32
AN:
152160
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000676
AC:
17
AN:
251466
Hom.:
0
AF XY:
0.0000662
AC XY:
9
AN XY:
135904
show subpopulations
Gnomad AFR exome
AF:
0.000800
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000163
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000301
AC:
44
AN:
1461816
Hom.:
0
Cov.:
37
AF XY:
0.0000220
AC XY:
16
AN XY:
727214
show subpopulations
Gnomad4 AFR exome
AF:
0.000478
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000655
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.000236
AC:
36
AN:
152278
Hom.:
0
Cov.:
32
AF XY:
0.000242
AC XY:
18
AN XY:
74458
show subpopulations
Gnomad4 AFR
AF:
0.000818
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000230
Hom.:
0
Bravo
AF:
0.000215
ESP6500AA
AF:
0.000681
AC:
3
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000107
AC:
13

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 GeneticsMay 06, 2022The c.40C>T (p.L14F) alteration is located in exon 1 (coding exon 1) of the MS4A6E gene. This alteration results from a C to T substitution at nucleotide position 40, causing the leucine (L) at amino acid position 14 to be replaced by a phenylalanine (F). 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
0.12
BayesDel_addAF
Benign
-0.59
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
16
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0091
T
Eigen
Benign
-0.59
Eigen_PC
Benign
-0.81
FATHMM_MKL
Benign
0.015
N
LIST_S2
Benign
0.78
T
M_CAP
Benign
0.0058
T
MetaRNN
Benign
0.053
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.8
L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-2.2
N
REVEL
Benign
0.13
Sift
Benign
0.11
T
Sift4G
Uncertain
0.018
D
Polyphen
0.97
D
Vest4
0.30
MVP
0.043
MPC
0.26
ClinPred
0.059
T
GERP RS
-0.23
Varity_R
0.069
gMVP
0.26

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: rs149427434; hg19: chr11-60102408; API