chr9-21815515-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PP3_StrongBS2
The NM_002451.4(MTAP):c.116G>T(p.Gly39Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000125 in 1,605,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
MTAP
NM_002451.4 missense
NM_002451.4 missense
Scores
13
3
2
Clinical Significance
Conservation
PhyloP100: 5.98
Genes affected
MTAP (HGNC:7413): (methylthioadenosine phosphorylase) This gene encodes an enzyme that plays a major role in polyamine metabolism and is important for the salvage pathway of both adenine and methionine. The encoded enzyme is deficient in many cancers. Multiple alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Sep 2021]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.979
BS2
?
High AC in GnomAdExome at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MTAP | NM_002451.4 | c.116G>T | p.Gly39Val | missense_variant | 2/8 | ENST00000644715.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MTAP | ENST00000644715.2 | c.116G>T | p.Gly39Val | missense_variant | 2/8 | NM_002451.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151458Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000240 AC: 6AN: 250270Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135246
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GnomAD4 exome AF: 0.0000124 AC: 18AN: 1454124Hom.: 0 Cov.: 28 AF XY: 0.00000967 AC XY: 7AN XY: 723796
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GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151458Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 73860
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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 | May 17, 2023 | The c.116G>T (p.G39V) alteration is located in exon 2 (coding exon 2) of the MTAP gene. This alteration results from a G to T substitution at nucleotide position 116, causing the glycine (G) at amino acid position 39 to be replaced by a valine (V). 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
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Pathogenic
D;D;D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;.;H;H
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
T
PROVEAN
Pathogenic
D;.;.;.
REVEL
Pathogenic
Sift
Uncertain
D;.;.;.
Sift4G
Pathogenic
D;D;.;D
Polyphen
D;P;D;.
Vest4
MutPred
0.95
.;Loss of sheet (P = 0.0315);.;.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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