chr3-52525085-C-A
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001134231.2(NT5DC2):c.1225G>T(p.Gly409Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000019 in 1,581,232 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 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000084 ( 0 hom. )
Consequence
NT5DC2
NM_001134231.2 missense
NM_001134231.2 missense
Scores
12
4
3
Clinical Significance
Conservation
PhyloP100: 7.79
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.956
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NT5DC2 | NM_001134231.2 | c.1225G>T | p.Gly409Cys | missense_variant | 12/14 | ENST00000422318.7 | |
NT5DC2 | NM_022908.3 | c.1114G>T | p.Gly372Cys | missense_variant | 12/14 | ||
NT5DC2 | XM_006713303.4 | c.1225G>T | p.Gly409Cys | missense_variant | 12/14 | ||
NT5DC2 | XM_047448760.1 | c.1114G>T | p.Gly372Cys | missense_variant | 12/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NT5DC2 | ENST00000422318.7 | c.1225G>T | p.Gly409Cys | missense_variant | 12/14 | 5 | NM_001134231.2 | P2 |
Frequencies
GnomAD3 genomes AF: 0.000121 AC: 18AN: 149258Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000199 AC: 4AN: 200616Hom.: 0 AF XY: 0.0000364 AC XY: 4AN XY: 110004
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GnomAD4 exome AF: 0.00000838 AC: 12AN: 1431888Hom.: 0 Cov.: 57 AF XY: 0.00000845 AC XY: 6AN XY: 710152
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GnomAD4 genome AF: 0.000121 AC: 18AN: 149344Hom.: 0 Cov.: 32 AF XY: 0.0000686 AC XY: 5AN XY: 72848
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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 | Jun 16, 2023 | The c.1225G>T (p.G409C) alteration is located in exon 12 (coding exon 12) of the NT5DC2 gene. This alteration results from a G to T substitution at nucleotide position 1225, causing the glycine (G) at amino acid position 409 to be replaced by a cysteine (C). 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
Benign
T;T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
.;M;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D;D
Sift4G
Pathogenic
D;D;D;D
Polyphen
1.0
.;D;.;.
Vest4
0.94, 0.95, 0.94
MutPred
0.85
.;Gain of catalytic residue at W373 (P = 0.0475);.;.;
MVP
MPC
1.1
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
DS_AG_spliceai
Position offset: -13
Find out detailed SpliceAI scores and Pangolin per-transcript scores at