3-66221177-T-C

Position:

• chr3-66221177-T-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001379210.1(SLC25A26):​c.33+50T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0137 in 1,497,838 control chromosomes in the GnomAD database, including 220 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (30 hom., cov: 33)
  • Exomes 𝑓: 0.014 (190 hom.)
• Consequence: SLC25A26 NM_001379210.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.46

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 3-66221177-T-C is Benign according to our data. Variant chr3-66221177-T-C is described in ClinVar as [Benign]. Clinvar id is 673805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A26	NM_001379210.1	c.33+50T>C		intron_variant		ENST00000354883.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A26	ENST00000354883.11	c.33+50T>C		intron_variant		2	NM_001379210.1	P1

Frequencies

GnomAD3 genomes AF: 0.0115 AC: 1757 AN: 152192 Hom.: 30 Cov.: 33

Gnomad AFR AF: 0.00275

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00595

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00601

Gnomad FIN AF: 0.0540

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0136

Gnomad OTH AF: 0.0100

GnomAD3 exomes AF: 0.0103 AC: 1105 AN: 107628 Hom.: 10 AF XY: 0.00967 AC XY: 571 AN XY: 59074

Gnomad AFR exome AF: 0.00159

Gnomad AMR exome AF: 0.00476

Gnomad ASJ exome AF: 0.00148

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00711

Gnomad FIN exome AF: 0.0494

Gnomad NFE exome AF: 0.0135

Gnomad OTH exome AF: 0.00984

GnomAD4 exome AF: 0.0139 AC: 18751 AN: 1345528 Hom.: 190 Cov.: 27 AF XY: 0.0135 AC XY: 8937 AN XY: 664266

Gnomad4 AFR exome AF: 0.00203

Gnomad4 AMR exome AF: 0.00519

Gnomad4 ASJ exome AF: 0.00144

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00688

Gnomad4 FIN exome AF: 0.0441

Gnomad4 NFE exome AF: 0.0149

Gnomad4 OTH exome AF: 0.0112

GnomAD4 genome AF: 0.0115 AC: 1758 AN: 152310 Hom.: 30 Cov.: 33 AF XY: 0.0129 AC XY: 961 AN XY: 74470

Gnomad4 AFR AF: 0.00274

Gnomad4 AMR AF: 0.00594

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00622

Gnomad4 FIN AF: 0.0540

Gnomad4 NFE AF: 0.0136

Gnomad4 OTH AF: 0.00992

Alfa AF: 0.0121 Hom.: 5

Bravo AF: 0.00835

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.74
CADD	Benign	0.55
DANN	Benign	0.55
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: rs138215846; hg19: chr3-66271603;