13-45401092-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T202I) has been classified as Uncertain significance.

• 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
• 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: Uncertain_significance. The variant received 3 ACMG points.

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

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.605C>A	p.Thr202Asn	missense	Exon 7 of 10	NP_001010875.1	Q5SVS4-1
	SLC25A30	NM_001286806.2		c.452C>A	p.Thr151Asn	missense	Exon 6 of 9	NP_001273735.1	Q5SVS4-2
	SLC25A30	NM_001286807.2		c.380C>A	p.Thr127Asn	missense	Exon 7 of 10	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.605C>A	p.Thr202Asn	missense	Exon 7 of 10	ENSP00000429168.1	Q5SVS4-1
	SLC25A30	ENST00000310862.11	TSL:1	n.*343C>A		non_coding_transcript_exon	Exon 7 of 10	ENSP00000311856.7	D6RJI0
	SLC25A30	ENST00000310862.11	TSL:1	n.*343C>A		3_prime_UTR	Exon 7 of 10	ENSP00000311856.7	D6RJI0

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

⚠️ 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: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44712

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111064

Other (OTH) AF: 0.00 AC: 0 AN: 60334

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.066	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	1.8	L
PhyloP100		9.5
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.40
Sift	Benign	0.41	T
Sift4G	Benign	0.27	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
Mutation Taster		=77/23	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: rs773340547; hg19: chr13-45975227;