9-128091211-A-G

Position:

• chr9-128091211-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330988.2(SLC25A25):​c.262-9885A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 155,312 control chromosomes in the GnomAD database, including 44,962 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 0.74 (43802 hom., cov: 31)
  • Exomes 𝑓: 0.84 (1160 hom.)
• Consequence: SLC25A25 NM_001330988.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0970

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A25	NM_001330988.2	c.262-9885A>G		intron_variant		ENST00000373069.10
SLC25A25	NM_001006641.4	c.262-9885A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A25	ENST00000373069.10	c.262-9885A>G		intron_variant		5	NM_001330988.2
SLC25A25	ENST00000373068.6	c.262-9885A>G		intron_variant		1
	ENST00000453870.1	n.523T>C		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.743 AC: 112968 AN: 151956 Hom.: 43794 Cov.: 31

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.826

Gnomad AMR AF: 0.767

Gnomad ASJ AF: 0.849

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.735

Gnomad FIN AF: 0.882

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.851

Gnomad OTH AF: 0.757

GnomAD4 exome AF: 0.843 AC: 2730 AN: 3238 Hom.: 1160 Cov.: 3 AF XY: 0.860 AC XY: 1348 AN XY: 1568

Gnomad4 AFR exome AF: 0.419

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 0.800

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.742

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.856

Gnomad4 OTH exome AF: 0.852

GnomAD4 genome AF: 0.743 AC: 113000 AN: 152074 Hom.: 43802 Cov.: 31 AF XY: 0.744 AC XY: 55303 AN XY: 74348

Gnomad4 AFR AF: 0.502

Gnomad4 AMR AF: 0.768

Gnomad4 ASJ AF: 0.849

Gnomad4 EAS AF: 0.811

Gnomad4 SAS AF: 0.736

Gnomad4 FIN AF: 0.882

Gnomad4 NFE AF: 0.851

Gnomad4 OTH AF: 0.754

Alfa AF: 0.782 Hom.: 7000

Bravo AF: 0.725

Asia WGS AF: 0.738 AC: 2571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.3
DANN	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10819354; hg19: chr9-130853490;