NM_001330988.2:c.262-12496G>A

Variant names:

• chr9-128088600-G-A
• rs6478815
• NM_001330988.2:c.262-12496G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330988.2(SLC25A25):​c.262-12496G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.952 in 152,260 control chromosomes in the GnomAD database, including 69,372 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.95 (69372 hom., cov: 32)
• Consequence: SLC25A25 NM_001330988.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0210
• Publications: 5 publications found

Genes affected

SLC25A25 (HGNC:20663): (solute carrier family 25 member 25) The protein encoded by this gene belongs to the family of calcium-binding mitochondrial carriers, with a characteristic mitochondrial carrier domain at the C-terminus. These proteins are found in the inner membranes of mitochondria, and function as transport proteins. They shuttle metabolites, nucleotides and cofactors through the mitochondrial membrane and thereby connect and/or regulate cytoplasm and matrix functions. This protein may function as an ATP-Mg/Pi carrier that mediates the transport of Mg-ATP in exchange for phosphate, and likely responsible for the net uptake or efflux of adenine nucleotides into or from the mitochondria. Alternatively spliced transcript variants encoding different isoforms with a common C-terminus but variable N-termini have been described for this gene. [provided by RefSeq, Jul 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A25	NM_001330988.2	c.262-12496G>A		intron_variant	Intron 1 of 10	ENST00000373069.10	NP_001317917.1
SLC25A25	NM_001006641.4	c.262-12496G>A		intron_variant	Intron 1 of 9		NP_001006642.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A25	ENST00000373069.10	c.262-12496G>A		intron_variant	Intron 1 of 10	5	NM_001330988.2	ENSP00000362160.5
SLC25A25	ENST00000373068.6	c.262-12496G>A		intron_variant	Intron 1 of 9	1		ENSP00000362159.2

Frequencies

GnomAD3 genomes AF: 0.952 AC: 144783 AN: 152142 Hom.: 69319 Cov.: 32

Gnomad AFR AF: 0.832

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.981

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.994

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.962

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.952 AC: 144892 AN: 152260 Hom.: 69372 Cov.: 32 AF XY: 0.953 AC XY: 70973 AN XY: 74454

African (AFR) AF: 0.833 AC: 34569 AN: 41518

American (AMR) AF: 0.981 AC: 14994 AN: 15286

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5176 AN: 5176

South Asian (SAS) AF: 0.999 AC: 4824 AN: 4828

European-Finnish (FIN) AF: 1.00 AC: 10622 AN: 10622

Middle Eastern (MID) AF: 0.993 AC: 292 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 68000 AN: 68042

Other (OTH) AF: 0.963 AC: 2031 AN: 2110

Alfa AF: 0.985 Hom.: 106868

Bravo AF: 0.945

Asia WGS AF: 0.992 AC: 3451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.9
DANN	Benign	0.61
PhyloP100		0.021
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6478815; hg19: chr9-130850879;