13-45395979-A-T

Variant names:

• chr13-45395979-A-T
• NM_001010875.4:c.871T>A

Variant summary

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

The NM_001010875.4(SLC25A30):​c.871T>A​(p.Leu291Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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: 32)
• Consequence: SLC25A30 NM_001010875.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.61

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=0.16865933).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A30	NM_001010875.4	c.871T>A	p.Leu291Met	missense_variant	Exon 10 of 10	ENST00000519676.6	NP_001010875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A30	ENST00000519676.6	c.871T>A	p.Leu291Met	missense_variant	Exon 10 of 10	1	NM_001010875.4	ENSP00000429168.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 13, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.871T>A (p.L291M) alteration is located in exon 10 (coding exon 9) of the SLC25A30 gene. This alteration results from a T to A substitution at nucleotide position 871, causing the leucine (L) at amino acid position 291 to be replaced by a methionine (M). 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	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.028	T;.
Eigen	Benign	0.12
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.63	T;T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.31	T
MutationAssessor	Benign	0.90	L;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.18	N;N
REVEL	Benign	0.26
Sift	Uncertain	0.023	D;D
Sift4G	Uncertain	0.022	D;D
Polyphen		0.92	P;.
Vest4		0.13
MutPred		0.52		Gain of methylation at K287 (P = 0.0516);.;
MVP		0.72
MPC		0.27
ClinPred		0.76	D
GERP RS		5.5
Varity_R		0.094
gMVP		0.64

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: chr13-45970114;