chr11-60175517-G-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_022349.4(MS4A6A):c.434C>A(p.Ala145Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,613,968 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000015 ( 0 hom. )
Consequence
MS4A6A
NM_022349.4 missense
NM_022349.4 missense
Scores
1
6
11
Clinical Significance
Conservation
PhyloP100: 1.18
Genes affected
MS4A6A (HGNC:13375): (membrane spanning 4-domains A6A) 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 11q12.1, among a cluster of family members. Alternative splicing of this gene results in several transcript variants that encode different protein isoforms. [provided by RefSeq, Oct 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MS4A6A | NM_022349.4 | c.434C>A | p.Ala145Asp | missense_variant | 5/6 | ENST00000528851.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MS4A6A | ENST00000528851.6 | c.434C>A | p.Ala145Asp | missense_variant | 5/6 | 1 | NM_022349.4 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152184Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251386Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135870
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GnomAD4 exome AF: 0.0000151 AC: 22AN: 1461784Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7AN XY: 727198
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GnomAD4 genome AF: 0.0000394 AC: 6AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74342
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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 submitter | clinical testing | Ambry Genetics | Feb 27, 2024 | The c.434C>A (p.A145D) alteration is located in exon 5 (coding exon 4) of the MS4A6A gene. This alteration results from a C to A substitution at nucleotide position 434, causing the alanine (A) at amino acid position 145 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;T;.;T;T
M_CAP
Benign
T
MetaRNN
Uncertain
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;.;.;.;.
MutationTaster
Benign
N;N;N;N;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D;D;D;D;.;D
REVEL
Benign
Sift
Uncertain
D;D;D;D;D;.;D
Sift4G
Benign
T;D;T;T;T;T;D
Polyphen
1.0
.;D;D;D;.;.;.
Vest4
MVP
MPC
0.38
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at