13-45405897-A-G

Variant names:

• chr13-45405897-A-G
• rs754013548
• NM_001010875.4:c.293T>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001010875.4(SLC25A30):​c.293T>C​(p.Ile98Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: SLC25A30 NM_001010875.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.87

Genes affected

SLC25A30 (HGNC:27371): (solute carrier family 25 member 30) Although the outer mitochondrial membrane is permeable to many small metabolites, transport of solutes across the inner mitochondrial membrane is achieved by members of the mitochondrial carrier protein family, such as SLC25A30 (Haguenauer et al., 2005 [PubMed 15809292]).[supplied by OMIM, Mar 2008]

TPT1-AS1 (HGNC:43686): (TPT1 antisense RNA 1) Biomarker of malignant astrocytoma. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08677396).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A30	NM_001010875.4	c.293T>C	p.Ile98Thr	missense_variant	Exon 4 of 10	ENST00000519676.6	NP_001010875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A30	ENST00000519676.6	c.293T>C	p.Ile98Thr	missense_variant	Exon 4 of 10	1	NM_001010875.4	ENSP00000429168.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000795 AC: 2 AN: 251420 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135888

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461824 Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4 AN XY: 727216

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 27, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.293T>C (p.I98T) alteration is located in exon 4 (coding exon 3) of the SLC25A30 gene. This alteration results from a T to C substitution at nucleotide position 293, causing the isoleucine (I) at amino acid position 98 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	Benign	0.11
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	21
DANN	Benign	0.38
DEOGEN2	Benign	0.11	T;.;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.99
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.76	T;T;T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.087	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.38	N;.;.;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.4	N;N;N;N
REVEL	Benign	0.25
Sift	Benign	0.27	T;T;T;T
Sift4G	Benign	0.55	T;T;.;.
Polyphen		0.0	B;.;.;.
Vest4		0.35
MutPred		0.43		Gain of disorder (P = 0.0134);.;.;.;
MVP		0.31
MPC		0.34
ClinPred		0.12	T
GERP RS		1.6
Varity_R		0.047
gMVP		0.80

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

LitVar

Other links and lift over

dbSNP: rs754013548; hg19: chr13-45980032;