NM_001379210.1:c.454-4951T>C

Variant names:

• chr3-66341413-T-C
• rs332364
• NM_001379210.1:c.454-4951T>C

Variant summary

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

The NM_001379210.1(SLC25A26):​c.454-4951T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,928 control chromosomes in the GnomAD database, including 13,747 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 0.37 (13747 hom., cov: 32)
• Consequence: SLC25A26 NM_001379210.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158
• Publications: 4 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A26	NM_001379210.1	c.454-4951T>C		intron_variant	Intron 5 of 9	ENST00000354883.11	NP_001366139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A26	ENST00000354883.11	c.454-4951T>C		intron_variant	Intron 5 of 9	2	NM_001379210.1	ENSP00000346955.6

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56051 AN: 151810 Hom.: 13693 Cov.: 32

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.339

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

GnomAD4 genome AF: 0.370 AC: 56180 AN: 151928 Hom.: 13747 Cov.: 32 AF XY: 0.377 AC XY: 28012 AN XY: 74246

African (AFR) AF: 0.649 AC: 26903 AN: 41430

American (AMR) AF: 0.423 AC: 6452 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 745 AN: 3468

East Asian (EAS) AF: 0.698 AC: 3603 AN: 5162

South Asian (SAS) AF: 0.463 AC: 2231 AN: 4814

European-Finnish (FIN) AF: 0.275 AC: 2907 AN: 10560

Middle Eastern (MID) AF: 0.205 AC: 60 AN: 292

European-Non Finnish (NFE) AF: 0.183 AC: 12419 AN: 67916

Other (OTH) AF: 0.346 AC: 732 AN: 2114

Alfa AF: 0.227 Hom.: 8116

Bravo AF: 0.393

Asia WGS AF: 0.598 AC: 2070 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.1
DANN	Benign	0.83
PhyloP100		-0.16

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: rs332364; hg19: chr3-66391837;