chr14-100292417-G-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001039355.3(SLC25A29):​c.778C>A​(p.Pro260Thr) variant causes a missense change involving the alteration of a conserved nucleotide. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SLC25A29
NM_001039355.3 missense

Scores

13
5
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.51
Variant links:
Genes affected
SLC25A29 (HGNC:20116): (solute carrier family 25 member 29) This gene encodes a nuclear-encoded mitochondrial protein that is a member of the large family of solute carrier family 25 (SLC25) mitochondrial transporters. The members of this superfamily are involved in numerous metabolic pathways and cell functions. This gene product was previously reported to be a mitochondrial carnitine-acylcarnitine-like (CACL) translocase (PMID:128829710) or an ornithine transporter (designated ORNT3, PMID:19287344), however, a recent study characterized the main role of this protein as a mitochondrial transporter of basic amino acids, with a preference for arginine and lysine (PMID:24652292). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Apr 2014]

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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, 0.941

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC25A29NM_001039355.3 linkuse as main transcriptc.778C>A p.Pro260Thr missense_variant 4/4 ENST00000359232.8 NP_001034444.1 Q8N8R3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC25A29ENST00000359232.8 linkuse as main transcriptc.778C>A p.Pro260Thr missense_variant 4/41 NM_001039355.3 ENSP00000352167.3 Q8N8R3-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1425492
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
706336
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

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 submitterclinical testingAmbry GeneticsOct 26, 2022The c.778C>A (p.P260T) alteration is located in exon 4 (coding exon 4) of the SLC25A29 gene. This alteration results from a C to A substitution at nucleotide position 778, causing the proline (P) at amino acid position 260 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.91
BayesDel_addAF
Pathogenic
0.45
D
BayesDel_noAF
Pathogenic
0.41
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.53
D;.;.;.
Eigen
Pathogenic
1.0
Eigen_PC
Pathogenic
0.95
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.97
D;.;.;D
M_CAP
Uncertain
0.27
D
MetaRNN
Pathogenic
0.94
D;D;D;D
MetaSVM
Pathogenic
0.80
D
MutationAssessor
Pathogenic
3.1
M;.;.;.
PrimateAI
Pathogenic
0.82
D
PROVEAN
Pathogenic
-7.6
D;D;D;D
REVEL
Pathogenic
0.92
Sift
Pathogenic
0.0
D;D;D;D
Sift4G
Uncertain
0.0050
D;D;D;D
Polyphen
1.0
D;.;.;.
Vest4
0.90
MutPred
0.80
Gain of catalytic residue at T265 (P = 0.0351);.;.;.;
MVP
0.99
MPC
1.0
ClinPred
1.0
D
GERP RS
5.6
Varity_R
0.86
gMVP
0.95

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-100758754; API