rs332389

chr3-66360790-G-A

Variant summary

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

The NM_001379210.1(SLC25A26):c.499-2070G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 152,080 control chromosomes in the GnomAD database, including 22,533 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 0.52 (22533 hom., cov: 33)
• Consequence: SLC25A26 NM_001379210.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.986

Genes affected

SLC25A26 (HGNC:20661): (solute carrier family 25 member 26) This gene is a member of the mitochondrial carrier family which includes nuclear-encoded transporters localized on the inner mitochondrial membranes. Members of the family transport important small molecules across the mitochondrial inner membrane. This protein is involved in the transport of S-adenosylmethionine (SAM) into the mitochondria. Mutations in this gene are associated with combined oxidative phosphorylation deficiency 28. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A26	NM_001379210.1	c.499-2070G>A		intron_variant		ENST00000354883.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A26	ENST00000354883.11	c.499-2070G>A		intron_variant		2	NM_001379210.1	P1

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79535 AN: 151962 Hom.: 22479 Cov.: 33

Gnomad AFR AF: 0.731

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.680

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.524 AC: 79648 AN: 152080 Hom.: 22533 Cov.: 33 AF XY: 0.529 AC XY: 39311 AN XY: 74338

Gnomad4 AFR AF: 0.731

Gnomad4 AMR AF: 0.566

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.679

Gnomad4 SAS AF: 0.559

Gnomad4 FIN AF: 0.447

Gnomad4 NFE AF: 0.397

Gnomad4 OTH AF: 0.511

Alfa AF: 0.438 Hom.: 7253

Bravo AF: 0.542

Asia WGS AF: 0.633 AC: 2198 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.084
Dann	Benign	0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs332389; hg19: chr3-66411214;