rs1553253990
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PM1PM2PM5PP3_StrongPP5_Very_Strong
The NM_013386.5(SLC25A24):c.649C>T(p.Arg217Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R217H) has been classified as Pathogenic.
Frequency
Genomes: not found (cov: 33)
Consequence
SLC25A24
NM_013386.5 missense
NM_013386.5 missense
Scores
12
4
1
Clinical Significance
Conservation
PhyloP100: 4.03
Genes affected
SLC25A24 (HGNC:20662): (solute carrier family 25 member 24) This gene encodes a carrier protein that transports ATP-Mg exchanging it for phosphate. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 ACMG points.
PM1
?
In a topological_domain Mitochondrial matrix (size 36) in uniprot entity SCMC1_HUMAN there are 6 pathogenic changes around while only 0 benign (100%) in NM_013386.5
PM2
?
Very rare variant in population databases, with high coverage;
PM5
?
Other missense variant is known to change same aminoacid residue: Variant chr1-108157481-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 370032.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.941
PP5
?
Variant 1-108157482-G-A is Pathogenic according to our data. Variant chr1-108157482-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 369980.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-108157482-G-A is described in UniProt as null. Variant chr1-108157482-G-A is described in Lovd as [Pathogenic]. Variant chr1-108157482-G-A is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC25A24 | NM_013386.5 | c.649C>T | p.Arg217Cys | missense_variant | 5/10 | ENST00000565488.6 | |
SLC25A24 | NM_213651.3 | c.592C>T | p.Arg198Cys | missense_variant | 5/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC25A24 | ENST00000565488.6 | c.649C>T | p.Arg217Cys | missense_variant | 5/10 | 1 | NM_013386.5 | P1 | |
SLC25A24 | ENST00000370041.4 | c.592C>T | p.Arg198Cys | missense_variant | 5/10 | 1 | |||
SLC25A24 | ENST00000648874.1 | c.649C>T | p.Arg217Cys | missense_variant, NMD_transcript_variant | 5/11 | ||||
SLC25A24 | ENST00000264128.13 | c.*228C>T | 3_prime_UTR_variant, NMD_transcript_variant | 4/9 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Fontaine progeroid syndrome Pathogenic:3
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 26, 2018 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | May 15, 2023 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | - | The de novo variant was identified at the same protein position as the variant reported as de novo in three independent cases with Petty syndrome. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MutPred
Loss of MoRF binding (P = 0.0205);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at