rs332389

Variant names:

• chr3-66360790-G-A
• rs332389
• NM_001379210.1:c.499-2070G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

SLC25A26 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• combined oxidative phosphorylation deficiency 28

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SLC25A26	NM_001379210.1	c.499-2070G>A		intron_variant	Intron 6 of 9	ENST00000354883.11	NP_001366139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A26	ENST00000354883.11	c.499-2070G>A		intron_variant	Intron 6 of 9	2	NM_001379210.1	ENSP00000346955.6

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

African (AFR) AF: 0.731 AC: 30326 AN: 41476

American (AMR) AF: 0.566 AC: 8641 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1354 AN: 3466

East Asian (EAS) AF: 0.679 AC: 3521 AN: 5182

South Asian (SAS) AF: 0.559 AC: 2695 AN: 4822

European-Finnish (FIN) AF: 0.447 AC: 4730 AN: 10572

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.397 AC: 26967 AN: 67966

Other (OTH) AF: 0.511 AC: 1080 AN: 2114

Alfa AF: 0.438 Hom.: 8140

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
PhyloP100		-0.99

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: rs332389; hg19: chr3-66411214;