chr11-60334908-C-T

Variant summary

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

The NM_139249.4(MS4A6E):​c.13C>T​(p.Pro5Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

MS4A6E
NM_139249.4 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.283
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 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=0.086325616).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MS4A6ENM_139249.4 linkuse as main transcriptc.13C>T p.Pro5Ser missense_variant 2/5 ENST00000684409.1
MS4A6ENR_170614.1 linkuse as main transcriptn.181C>T non_coding_transcript_exon_variant 2/6
MS4A6ENR_170615.1 linkuse as main transcriptn.181C>T non_coding_transcript_exon_variant 2/5
MS4A6ENR_170616.1 linkuse as main transcriptn.181C>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.13C>T p.Pro5Ser missense_variant 2/5 NM_139249.4 P1
MS4A6EENST00000300182.8 linkuse as main transcriptc.13C>T p.Pro5Ser missense_variant 1/41 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461734
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
727182
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000630
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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 GeneticsMar 27, 2023The c.13C>T (p.P5S) 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 13, causing the proline (P) at amino acid position 5 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
0.090
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.75
CADD
Benign
4.5
DANN
Uncertain
0.99
DEOGEN2
Benign
0.039
T
Eigen
Benign
-0.77
Eigen_PC
Benign
-0.99
FATHMM_MKL
Benign
0.0062
N
LIST_S2
Benign
0.66
T
M_CAP
Benign
0.0065
T
MetaRNN
Benign
0.086
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Uncertain
2.1
M
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.24
T
PROVEAN
Pathogenic
-4.5
D
REVEL
Benign
0.063
Sift
Benign
0.20
T
Sift4G
Benign
0.25
T
Polyphen
0.98
D
Vest4
0.044
MutPred
0.10
Loss of glycosylation at T2 (P = 0.057);
MVP
0.043
MPC
0.25
ClinPred
0.77
D
GERP RS
0.13
Varity_R
0.043
gMVP
0.21

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-60102381; API