11-60386730-G-A
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_021201.5(MS4A7):c.296G>A(p.Gly99Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000754 in 1,613,022 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00036 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00080 ( 2 hom. )
Consequence
MS4A7
NM_021201.5 missense
NM_021201.5 missense
Scores
5
7
7
Clinical Significance
Conservation
PhyloP100: 4.00
Genes affected
MS4A7 (HGNC:13378): (membrane spanning 4-domains A7) This gene encodes a member of the membrane-spanning 4A gene family, members of which are characterized by common structural features and similar intron/exon splice boundaries and display unique expression patterns in hematopoietic cells and nonlymphoid tissues. This family member is associated with mature cellular function in the monocytic lineage, and it may be a component of a receptor complex involved in signal transduction. This gene is localized to 11q12, in a cluster of other family members. At least four alternatively spliced transcript variants encoding two distinct isoforms have been observed. [provided by RefSeq, Jul 2008]
MS4A14 (HGNC:30706): (membrane spanning 4-domains A14) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]
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 -4 ACMG points.
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MS4A7 | NM_021201.5 | c.296G>A | p.Gly99Glu | missense_variant | 4/7 | ENST00000300184.8 | |
MS4A7 | NM_206939.2 | c.296G>A | p.Gly99Glu | missense_variant | 4/7 | ||
MS4A7 | NM_206938.2 | c.161G>A | p.Gly54Glu | missense_variant | 3/6 | ||
MS4A7 | NM_206940.2 | c.161G>A | p.Gly54Glu | missense_variant | 3/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MS4A7 | ENST00000300184.8 | c.296G>A | p.Gly99Glu | missense_variant | 4/7 | 1 | NM_021201.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000361 AC: 55AN: 152194Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000399 AC: 100AN: 250872Hom.: 0 AF XY: 0.000420 AC XY: 57AN XY: 135602
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GnomAD4 exome AF: 0.000796 AC: 1162AN: 1460710Hom.: 2 Cov.: 29 AF XY: 0.000749 AC XY: 544AN XY: 726698
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GnomAD4 genome AF: 0.000361 AC: 55AN: 152312Hom.: 0 Cov.: 32 AF XY: 0.000389 AC XY: 29AN XY: 74490
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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 | Sep 17, 2021 | The c.296G>A (p.G99E) alteration is located in exon 4 (coding exon 3) of the MS4A7 gene. This alteration results from a G to A substitution at nucleotide position 296, causing the glycine (G) at amino acid position 99 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.;.;.
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T;.;T;T
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;.;.;.;.
MutationTaster
Benign
D;D;N;N;N
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;D
Sift4G
Pathogenic
D;D;D;D;D
Polyphen
D;D;D;D;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AL_spliceai
Position offset: -13
Find out detailed SpliceAI scores and Pangolin per-transcript scores at