3-66220872-C-A

Position:

• chr3-66220872-C-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_173471.4(SLC25A26):​c.-223C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0108 in 588,940 control chromosomes in the GnomAD database, including 143 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0095 (33 hom., cov: 32)
  • Exomes 𝑓: 0.011 (110 hom.)
• Consequence: SLC25A26 NM_173471.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.690

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 3-66220872-C-A is Benign according to our data. Variant chr3-66220872-C-A is described in ClinVar as [Benign]. Clinvar id is 1225345.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A26	NM_001164796.1	c.-330C>A		5_prime_UTR_variant	1/9
SLC25A26	NM_001350993.1	c.-574C>A		5_prime_UTR_variant	1/11
SLC25A26	NM_173471.4	c.-223C>A		5_prime_UTR_variant	2/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A26	ENST00000676754.1	c.-223C>A		5_prime_UTR_variant	2/11			P1
SLC25A26	ENST00000686511.1	c.-232+14C>A		intron_variant
SLC25A26	ENST00000690634.1	c.-232+14C>A		intron_variant, NMD_transcript_variant
SLC25A26	ENST00000689520.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.00949 AC: 1444 AN: 152164 Hom.: 33 Cov.: 32

Gnomad AFR AF: 0.00104

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.0744

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00820

Gnomad OTH AF: 0.00383

GnomAD4 exome AF: 0.0113 AC: 4931 AN: 436658 Hom.: 110 Cov.: 4 AF XY: 0.0105 AC XY: 2453 AN XY: 233520

Gnomad4 AFR exome AF: 0.00121

Gnomad4 AMR exome AF: 0.00171

Gnomad4 ASJ exome AF: 0.000872

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00215

Gnomad4 FIN exome AF: 0.0751

Gnomad4 NFE exome AF: 0.00834

Gnomad4 OTH exome AF: 0.00933

GnomAD4 genome AF: 0.00948 AC: 1444 AN: 152282 Hom.: 33 Cov.: 32 AF XY: 0.0119 AC XY: 888 AN XY: 74450

Gnomad4 AFR AF: 0.00103

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00186

Gnomad4 FIN AF: 0.0744

Gnomad4 NFE AF: 0.00820

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.00625 Hom.: 1

Bravo AF: 0.00385

Asia WGS AF: 0.00173 AC: 6 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

Sep 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.5
DANN	Benign	0.71

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: rs36139379; hg19: chr3-66271298;