13-45409023-G-T

Variant names:

• chr13-45409023-G-T
• rs368357937
• NM_001010875.4:c.116C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001010875.4(SLC25A30):​c.116C>A​(p.Thr39Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T39M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC25A30 NM_001010875.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.768
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.042053252).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010875.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A30	NM_001010875.4	MANE Select	c.116C>A	p.Thr39Lys	missense	Exon 3 of 10	NP_001010875.1	Q5SVS4-1
	SLC25A30	NM_001286806.2		c.-38C>A		5_prime_UTR	Exon 2 of 9	NP_001273735.1	Q5SVS4-2
	SLC25A30	NM_001286807.2		c.-14+2339C>A		intron	N/A	NP_001273736.1	B3KTE8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A30	ENST00000519676.6	TSL:1 MANE Select	c.116C>A	p.Thr39Lys	missense	Exon 3 of 10	ENSP00000429168.1	Q5SVS4-1
	SLC25A30	ENST00000310862.11	TSL:1	n.64+2339C>A		intron	N/A	ENSP00000311856.7	D6RJI0
	SLC25A30	ENST00000857533.1		c.116C>A	p.Thr39Lys	missense	Exon 3 of 10	ENSP00000527592.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460660 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726638

African (AFR) AF: 0.00 AC: 0 AN: 33432

American (AMR) AF: 0.00 AC: 0 AN: 44520

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39628

South Asian (SAS) AF: 0.00 AC: 0 AN: 86006

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111484

Other (OTH) AF: 0.00 AC: 0 AN: 60338

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	9.2
DANN	Benign	0.43
DEOGEN2	Benign	0.079	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.21	N
PhyloP100		0.77
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.15	N
REVEL	Benign	0.078
Sift	Benign	0.98	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.29
MutPred		0.39		Gain of MoRF binding (P = 0.0224)
MVP		0.27
MPC		0.33
ClinPred		0.019	T
GERP RS		-0.076
Varity_R		0.022
gMVP		0.74
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs368357937; hg19: chr13-45983158;