3-66236407-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001379210.1(SLC25A26):c.34-137G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 518,158 control chromosomes in the GnomAD database, including 15,044 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (6438 hom., cov: 31)
  • Exomes 𝑓: 0.20 (8606 hom.)
• Consequence: SLC25A26 NM_001379210.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0630

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 3-66236407-G-T is Benign according to our data. Variant chr3-66236407-G-T is described in ClinVar as [Benign]. Clinvar id is 683880.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A26	NM_001379210.1	c.34-137G>T		intron_variant		ENST00000354883.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A26	ENST00000354883.11	c.34-137G>T		intron_variant		2	NM_001379210.1	P1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41691 AN: 151392 Hom.: 6421 Cov.: 31

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.234

GnomAD4 exome AF: 0.204 AC: 74748 AN: 366646 Hom.: 8606 AF XY: 0.201 AC XY: 37318 AN XY: 185740

Gnomad4 AFR exome AF: 0.395

Gnomad4 AMR exome AF: 0.291

Gnomad4 ASJ exome AF: 0.134

Gnomad4 EAS exome AF: 0.106

Gnomad4 SAS exome AF: 0.107

Gnomad4 FIN exome AF: 0.344

Gnomad4 NFE exome AF: 0.198

Gnomad4 OTH exome AF: 0.210

GnomAD4 genome AF: 0.276 AC: 41744 AN: 151512 Hom.: 6438 Cov.: 31 AF XY: 0.278 AC XY: 20603 AN XY: 74024

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.131

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.360

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.231

Alfa AF: 0.183 Hom.: 641

Bravo AF: 0.278

Asia WGS AF: 0.163 AC: 570 AN: 3476

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

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	2.1
Dann	Benign	0.62

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: rs188291587; hg19: chr3-66286831;