chr1-108139072-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PP3_StrongBS2
The NM_013386.5(SLC25A24):c.1235G>A(p.Arg412His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000276 in 1,596,852 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 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000028 ( 0 hom. )
Consequence
SLC25A24
NM_013386.5 missense
NM_013386.5 missense
Scores
7
7
3
Clinical Significance
Conservation
PhyloP100: 7.83
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 Uncertain_significance. Variant got 0 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.956
BS2
High AC in GnomAdExome4 at 41 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC25A24 | NM_013386.5 | c.1235G>A | p.Arg412His | missense_variant | 9/10 | ENST00000565488.6 | |
SLC25A24 | NM_213651.3 | c.1178G>A | p.Arg393His | missense_variant | 9/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC25A24 | ENST00000565488.6 | c.1235G>A | p.Arg412His | missense_variant | 9/10 | 1 | NM_013386.5 | P1 | |
SLC25A24 | ENST00000370041.4 | c.1178G>A | p.Arg393His | missense_variant | 9/10 | 1 | |||
SLC25A24 | ENST00000264128.13 | c.*814G>A | 3_prime_UTR_variant, NMD_transcript_variant | 8/9 | 5 | ||||
SLC25A24 | ENST00000648874.1 | c.*556G>A | 3_prime_UTR_variant, NMD_transcript_variant | 10/11 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152130Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000210 AC: 5AN: 238644Hom.: 0 AF XY: 0.0000155 AC XY: 2AN XY: 129030
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GnomAD4 exome AF: 0.0000284 AC: 41AN: 1444722Hom.: 0 Cov.: 31 AF XY: 0.0000293 AC XY: 21AN XY: 717838
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152130Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74296
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 01, 2023 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 412 of the SLC25A24 protein (p.Arg412His). This variant is present in population databases (rs781747926, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with SLC25A24-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SLC25A24 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
T
PROVEAN
Uncertain
D;D
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MutPred
Gain of catalytic residue at Q416 (P = 0.0668);.;
MVP
MPC
ClinPred
D
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