9-128107279-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001330988.2(SLC25A25):c.1383G>A(p.Pro461=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00434 in 1,590,896 control chromosomes in the GnomAD database, including 257 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.023 (126 hom., cov: 33)
  • Exomes 𝑓: 0.0024 (131 hom.)
• Consequence: SLC25A25 NM_001330988.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -8.21

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

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 9-128107279-G-A is Benign according to our data. Variant chr9-128107279-G-A is described in ClinVar as [Benign]. Clinvar id is 711026.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-8.21 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A25	NM_001330988.2	c.1383G>A	p.Pro461=	synonymous_variant	11/11	ENST00000373069.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A25	ENST00000373069.10	c.1383G>A	p.Pro461=	synonymous_variant	11/11	5	NM_001330988.2

Frequencies

GnomAD3 genomes AF: 0.0228 AC: 3466 AN: 152172 Hom.: 125 Cov.: 33

Gnomad AFR AF: 0.0788

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00753

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.0215

GnomAD3 exomes AF: 0.00631 AC: 1517 AN: 240454 Hom.: 61 AF XY: 0.00452 AC XY: 587 AN XY: 129818

Gnomad AFR exome AF: 0.0831

Gnomad AMR exome AF: 0.00340

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000656

Gnomad SAS exome AF: 0.000174

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000304

Gnomad OTH exome AF: 0.00276

GnomAD4 exome AF: 0.00239 AC: 3432 AN: 1438606 Hom.: 131 Cov.: 34 AF XY: 0.00210 AC XY: 1495 AN XY: 711778

Gnomad4 AFR exome AF: 0.0828

Gnomad4 AMR exome AF: 0.00371

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000331

Gnomad4 SAS exome AF: 0.000296

Gnomad4 FIN exome AF: 0.0000382

Gnomad4 NFE exome AF: 0.000191

Gnomad4 OTH exome AF: 0.00437

GnomAD4 genome AF: 0.0228 AC: 3470 AN: 152290 Hom.: 126 Cov.: 33 AF XY: 0.0223 AC XY: 1663 AN XY: 74472

Gnomad4 AFR AF: 0.0787

Gnomad4 AMR AF: 0.00752

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000500

Gnomad4 OTH AF: 0.0213

Alfa AF: 0.0125 Hom.: 29

Bravo AF: 0.0256

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 16, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.17
Dann	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs16930267; hg19: chr9-130869558;