3-66221164-C-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.33+37C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00393 in 1,499,026 control chromosomes in the GnomAD database, including 193 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (109 hom., cov: 33)
  • Exomes 𝑓: 0.0020 (84 hom.)
• Consequence: SLC25A26 NM_001379210.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.381

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=-0.62).
• BP6: Variant 3-66221164-C-T is Benign according to our data. Variant chr3-66221164-C-T is described in ClinVar as [Benign]. Clinvar id is 673258.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.07 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A26	NM_001379210.1	c.33+37C>T		intron_variant		ENST00000354883.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A26	ENST00000354883.11	c.33+37C>T		intron_variant		2	NM_001379210.1	P1

Frequencies

GnomAD3 genomes AF: 0.0206 AC: 3132 AN: 152180 Hom.: 108 Cov.: 33

Gnomad AFR AF: 0.0723

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00550

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0129

GnomAD3 exomes AF: 0.00449 AC: 458 AN: 102016 Hom.: 14 AF XY: 0.00324 AC XY: 182 AN XY: 56164

Gnomad AFR exome AF: 0.0709

Gnomad AMR exome AF: 0.00436

Gnomad ASJ exome AF: 0.000912

Gnomad EAS exome AF: 0.000160

Gnomad SAS exome AF: 0.000160

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000162

Gnomad OTH exome AF: 0.00405

GnomAD4 exome AF: 0.00205 AC: 2758 AN: 1346728 Hom.: 84 Cov.: 30 AF XY: 0.00178 AC XY: 1186 AN XY: 664590

Gnomad4 AFR exome AF: 0.0738

Gnomad4 AMR exome AF: 0.00475

Gnomad4 ASJ exome AF: 0.000806

Gnomad4 EAS exome AF: 0.0000304

Gnomad4 SAS exome AF: 0.000437

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000220

Gnomad4 OTH exome AF: 0.00448

GnomAD4 genome AF: 0.0206 AC: 3136 AN: 152298 Hom.: 109 Cov.: 33 AF XY: 0.0192 AC XY: 1433 AN XY: 74474

Gnomad4 AFR AF: 0.0722

Gnomad4 AMR AF: 0.00549

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.0104 Hom.: 11

Bravo AF: 0.0232

Asia WGS AF: 0.00404 AC: 14 AN: 3478

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	-0.62
Cadd	Benign	8.6
Dann	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs141327145; hg19: chr3-66271590;