rs332379

Variant names:

• chr3-66370193-A-G
• rs332379
• NM_001379210.1:c.634-336A>G

Variant summary

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

The NM_001379210.1(SLC25A26):​c.634-336A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0741 in 152,284 control chromosomes in the GnomAD database, including 558 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 0.074 (558 hom., cov: 33)
• Consequence: SLC25A26 NM_001379210.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.443
• Publications: 0 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A26	NM_001379210.1	c.634-336A>G		intron_variant	Intron 8 of 9	ENST00000354883.11	NP_001366139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A26	ENST00000354883.11	c.634-336A>G		intron_variant	Intron 8 of 9	2	NM_001379210.1	ENSP00000346955.6

Frequencies

GnomAD3 genomes AF: 0.0741 AC: 11279 AN: 152166 Hom.: 558 Cov.: 33

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0679

Gnomad ASJ AF: 0.0375

Gnomad EAS AF: 0.0156

Gnomad SAS AF: 0.0329

Gnomad FIN AF: 0.0941

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0426

Gnomad OTH AF: 0.0664

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

GnomAD4 genome AF: 0.0741 AC: 11291 AN: 152284 Hom.: 558 Cov.: 33 AF XY: 0.0752 AC XY: 5602 AN XY: 74470

African (AFR) AF: 0.140 AC: 5831 AN: 41546

American (AMR) AF: 0.0677 AC: 1036 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0375 AC: 130 AN: 3470

East Asian (EAS) AF: 0.0158 AC: 82 AN: 5184

South Asian (SAS) AF: 0.0325 AC: 157 AN: 4826

European-Finnish (FIN) AF: 0.0941 AC: 998 AN: 10610

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0426 AC: 2900 AN: 68020

Other (OTH) AF: 0.0671 AC: 142 AN: 2116

Alfa AF: 0.0529 Hom.: 163

Bravo AF: 0.0754

Asia WGS AF: 0.0570 AC: 197 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.48
DANN	Benign	0.51
PhyloP100		-0.44

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: rs332379; hg19: chr3-66420617;