3-66220525-G-C

Position:

• chr3-66220525-G-C

Variant summary

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

The NM_173471.4(SLC25A26):​c.-353-217G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 151,804 control chromosomes in the GnomAD database, including 52,414 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.82 (52414 hom., cov: 33)
• Consequence: SLC25A26 NM_173471.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.413

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=-0.86).
• BP6: Variant 3-66220525-G-C is Benign according to our data. Variant chr3-66220525-G-C is described in ClinVar as [Benign]. Clinvar id is 683875.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A26	NM_173471.4	c.-353-217G>C		intron_variant			NP_775742.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A26	ENST00000676754.1	c.-353-217G>C		intron_variant				ENSP00000504323	P1

Frequencies

GnomAD3 genomes AF: 0.825 AC: 125093 AN: 151686 Hom.: 52402 Cov.: 33

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.952

Gnomad AMR AF: 0.820

Gnomad ASJ AF: 0.897

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.911

Gnomad FIN AF: 0.899

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.902

Gnomad OTH AF: 0.849

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

GnomAD4 genome AF: 0.824 AC: 125150 AN: 151804 Hom.: 52414 Cov.: 33 AF XY: 0.825 AC XY: 61196 AN XY: 74174

Gnomad4 AFR AF: 0.675

Gnomad4 AMR AF: 0.820

Gnomad4 ASJ AF: 0.897

Gnomad4 EAS AF: 0.697

Gnomad4 SAS AF: 0.911

Gnomad4 FIN AF: 0.899

Gnomad4 NFE AF: 0.902

Gnomad4 OTH AF: 0.848

Alfa AF: 0.823 Hom.: 2654

Bravo AF: 0.811

Asia WGS AF: 0.795 AC: 2767 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	-0.86
CADD	Benign	1.8
DANN	Benign	0.43

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: rs36162483; hg19: chr3-66270951;