3-66220743-T-A

Position:

• chr3-66220743-T-A

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.-352T>A variant causes a splice region, 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00927 in 389,416 control chromosomes in the GnomAD database, including 127 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (108 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (19 hom.)
• Consequence: SLC25A26 NM_173471.4 splice_region, 5_prime_UTR
• Scores: Splicing: ADA: 0.00005408
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.230

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=-0.71).
• BP6: Variant 3-66220743-T-A is Benign according to our data. Variant chr3-66220743-T-A is described in ClinVar as [Benign]. Clinvar id is 673257.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_001164796.1	c.-459T>A		5_prime_UTR_variant	1/9
SLC25A26	NM_001350993.1	c.-703T>A		5_prime_UTR_variant	1/11
SLC25A26	NM_173471.4	c.-352T>A		splice_region_variant, 5_prime_UTR_variant	2/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A26	ENST00000676754.1	c.-352T>A		splice_region_variant, 5_prime_UTR_variant	2/11			P1
SLC25A26	ENST00000686511.1	c.-347T>A		5_prime_UTR_variant	1/10
SLC25A26	ENST00000690634.1	c.-347T>A		5_prime_UTR_variant, NMD_transcript_variant	1/9

Frequencies

GnomAD3 genomes AF: 0.0206 AC: 3129 AN: 152036 Hom.: 107 Cov.: 32

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: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0134

GnomAD4 exome AF: 0.00200 AC: 475 AN: 237262 Hom.: 19 Cov.: 0 AF XY: 0.00170 AC XY: 214 AN XY: 125930

Gnomad4 AFR exome AF: 0.0686

Gnomad4 AMR exome AF: 0.00401

Gnomad4 ASJ exome AF: 0.000944

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000435

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000291

Gnomad4 OTH exome AF: 0.00421

GnomAD4 genome AF: 0.0206 AC: 3133 AN: 152154 Hom.: 108 Cov.: 32 AF XY: 0.0193 AC XY: 1433 AN XY: 74394

Gnomad4 AFR AF: 0.0722

Gnomad4 AMR AF: 0.00549

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.0133

Alfa AF: 0.0153 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	-0.71
CADD	Benign	3.5
DANN	Benign	0.36

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000054
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.070		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: rs141331547; hg19: chr3-66271169;