3-66236253-G-A

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.34-291G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 128,440 control chromosomes in the GnomAD database, including 1,562 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (1562 hom., cov: 25)
• Consequence: SLC25A26 NM_001379210.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.536

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=-0.91).
• BP6: Variant 3-66236253-G-A is Benign according to our data. Variant chr3-66236253-G-A is described in ClinVar as [Benign]. Clinvar id is 683879.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A26	NM_001379210.1	c.34-291G>A		intron_variant		ENST00000354883.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A26	ENST00000354883.11	c.34-291G>A		intron_variant		2	NM_001379210.1	P1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 18469 AN: 128386 Hom.: 1562 Cov.: 25

Gnomad AFR AF: 0.0843

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.0859

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.0913

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.144 AC: 18465 AN: 128440 Hom.: 1562 Cov.: 25 AF XY: 0.141 AC XY: 8556 AN XY: 60684

Gnomad4 AFR AF: 0.0841

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.0859

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.123

Alfa AF: 0.00558 Hom.: 3

Bravo AF: 0.131

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 16, 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	-0.91
Cadd	Benign	0.28
Dann	Benign	0.29

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: rs36197639; hg19: chr3-66286677;