3-66220821-C-G

Position:

• chr3-66220821-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_173471.4(SLC25A26):​c.-274C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0508 in 530,348 control chromosomes in the GnomAD database, including 926 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.063 (357 hom., cov: 32)
  • Exomes 𝑓: 0.046 (569 hom.)
• Consequence: SLC25A26 NM_173471.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.816

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 3-66220821-C-G is Benign according to our data. Variant chr3-66220821-C-G is described in ClinVar as [Benign]. Clinvar id is 672649.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A26	NM_001164796.1	c.-381C>G		5_prime_UTR_variant	1/9
SLC25A26	NM_001350993.1	c.-625C>G		5_prime_UTR_variant	1/11
SLC25A26	NM_001400711.1	c.-269C>G		5_prime_UTR_variant	1/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A26	ENST00000676754.1	c.-274C>G		5_prime_UTR_variant	2/11			P1
SLC25A26	ENST00000686511.1	c.-269C>G		5_prime_UTR_variant	1/10
SLC25A26	ENST00000690634.1	c.-269C>G		5_prime_UTR_variant, NMD_transcript_variant	1/9

Frequencies

GnomAD3 genomes AF: 0.0631 AC: 9600 AN: 152070 Hom.: 357 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0653

Gnomad ASJ AF: 0.0397

Gnomad EAS AF: 0.0926

Gnomad SAS AF: 0.0292

Gnomad FIN AF: 0.0516

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0415

Gnomad OTH AF: 0.0536

GnomAD4 exome AF: 0.0458 AC: 17325 AN: 378160 Hom.: 569 Cov.: 0 AF XY: 0.0443 AC XY: 8845 AN XY: 199666

Gnomad4 AFR exome AF: 0.0969

Gnomad4 AMR exome AF: 0.0693

Gnomad4 ASJ exome AF: 0.0376

Gnomad4 EAS exome AF: 0.105

Gnomad4 SAS exome AF: 0.0231

Gnomad4 FIN exome AF: 0.0565

Gnomad4 NFE exome AF: 0.0403

Gnomad4 OTH exome AF: 0.0463

GnomAD4 genome AF: 0.0631 AC: 9607 AN: 152188 Hom.: 357 Cov.: 32 AF XY: 0.0628 AC XY: 4669 AN XY: 74400

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.0651

Gnomad4 ASJ AF: 0.0397

Gnomad4 EAS AF: 0.0929

Gnomad4 SAS AF: 0.0288

Gnomad4 FIN AF: 0.0516

Gnomad4 NFE AF: 0.0415

Gnomad4 OTH AF: 0.0545

Alfa AF: 0.0623 Hom.: 48

Bravo AF: 0.0668

Asia WGS AF: 0.0740 AC: 255 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 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	-0.69
CADD	Benign	7.2
DANN	Benign	0.82

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: rs137909944; hg19: chr3-66271247;