chr13-45409045-G-C

Variant names:

• chr13-45409045-G-C
• rs370602370
• NM_001010875.4:c.94C>G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001010875.4(SLC25A30):​c.94C>G​(p.Arg32Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,457,730 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R32W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC25A30 NM_001010875.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.27
• 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_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.977

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.94C>G	p.Arg32Gly	missense	Exon 3 of 10	NP_001010875.1	Q5SVS4-1
	SLC25A30	NM_001286806.2		c.-60C>G		5_prime_UTR	Exon 2 of 9	NP_001273735.1	Q5SVS4-2
	SLC25A30	NM_001286807.2		c.-14+2317C>G		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.94C>G	p.Arg32Gly	missense	Exon 3 of 10	ENSP00000429168.1	Q5SVS4-1
	SLC25A30	ENST00000310862.11	TSL:1	n.64+2317C>G		intron	N/A	ENSP00000311856.7	D6RJI0
	SLC25A30	ENST00000857533.1		c.94C>G	p.Arg32Gly	missense	Exon 3 of 10	ENSP00000527592.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457730 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 725070

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33304

American (AMR) AF: 0.00 AC: 0 AN: 43756

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26016

East Asian (EAS) AF: 0.00 AC: 0 AN: 39592

South Asian (SAS) AF: 0.00 AC: 0 AN: 85220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53312

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110548

Other (OTH) AF: 0.00 AC: 0 AN: 60230

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00666416), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.45	D
BayesDel_noAF	Pathogenic	0.41
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.61	D
Eigen	Pathogenic	0.94
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Pathogenic	0.53	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Pathogenic	4.7	H
PhyloP100		6.3
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-6.2	D
REVEL	Pathogenic	0.93
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.95
MutPred		0.89		Loss of catalytic residue at R32 (P = 0.0769)
MVP		0.98
MPC		1.1
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.92
gMVP		0.98
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs370602370; hg19: chr13-45983180;