13-45401092-G-T

Variant names:

• chr13-45401092-G-T
• rs773340547
• NM_001010875.4:c.605C>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001010875.4(SLC25A30):​c.605C>A​(p.Thr202Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC25A30 NM_001010875.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.49

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.751

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A30	NM_001010875.4	c.605C>A	p.Thr202Asn	missense_variant	Exon 7 of 10	ENST00000519676.6	NP_001010875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A30	ENST00000519676.6	c.605C>A	p.Thr202Asn	missense_variant	Exon 7 of 10	1	NM_001010875.4	ENSP00000429168.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460654 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726746

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	20
DANN	Benign	0.54
DEOGEN2	Benign	0.16	T;.
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.062
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Benign	0.066	D
MetaRNN	Pathogenic	0.75	D;D
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	1.8	L;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.7	N;N
REVEL	Uncertain	0.40
Sift	Benign	0.41	T;T
Sift4G	Benign	0.27	T;T
Polyphen		0.041	B;.
Vest4		0.92
MutPred		0.57		Gain of catalytic residue at T202 (P = 0.094);.;
MVP		0.79
MPC		0.35
ClinPred		0.75	D
GERP RS		4.7
Varity_R		0.11
gMVP		0.87

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: rs773340547; hg19: chr13-45975227;