Genetic Variant SLC25A26:c.454-4951T>C (chr3-66341413-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001379210.1(SLC25A26):c.454-4951T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,928 control chromosomes in the GnomAD database, including 13,747 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.37 ( 13747 hom., cov: 32)

Consequence

SLC25A26
NM_001379210.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.158

Publications

4 publications found

Variant links:

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]

SLC25A26 Gene-Disease associations (from GenCC):

mitochondrial disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
combined oxidative phosphorylation deficiency 28
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet

SLC25A26 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.02).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379210.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC25A26	NM_001379210.1	MANE Select	c.454-4951T>C	intron	N/A	NP_001366139.1	Q70HW3-1
SLC25A26	NM_001400705.1		c.454-4951T>C	intron	N/A	NP_001387634.1
SLC25A26	NM_173471.4		c.454-4951T>C	intron	N/A	NP_775742.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC25A26	ENST00000354883.11	TSL:2 MANE Select	c.454-4951T>C	intron	N/A	ENSP00000346955.6	Q70HW3-1
SLC25A26	ENST00000336733.10	TSL:1	c.190-4951T>C	intron	N/A	ENSP00000336801.5	Q70HW3-2
SLC25A26	ENST00000464350.6	TSL:1	n.190-4951T>C	intron	N/A	ENSP00000432574.2	H0YCZ5

Frequencies

GnomAD3 genomes

AF:

0.369

AC:

56051

AN:

151810

Hom.:

13693

Cov.:

show subpopulations

Gnomad AFR

AF:

0.649

Gnomad AMI

AF:

0.140

Gnomad AMR

AF:

0.422

Gnomad ASJ

AF:

0.215

Gnomad EAS

AF:

0.698

Gnomad SAS

AF:

0.463

Gnomad FIN

AF:

0.275

Gnomad MID

AF:

0.194

Gnomad NFE

AF:

0.183

Gnomad OTH

AF:

0.339

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

GnomAD4 genome

AF:

0.370

AC:

56180

AN:

151928

Hom.:

13747

Cov.:

AF XY:

0.377

AC XY:

28012

AN XY:

74246

show subpopulations

African (AFR)

AF:

0.649

AC:

26903

AN:

41430

American (AMR)

AF:

0.423

AC:

6452

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.215

AC:

745

AN:

3468

East Asian (EAS)

AF:

0.698

AC:

3603

AN:

5162

South Asian (SAS)

AF:

0.463

AC:

2231

AN:

4814

European-Finnish (FIN)

AF:

0.275

AC:

2907

AN:

10560

Middle Eastern (MID)

AF:

0.205

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.183

AC:

12419

AN:

67916

Other (OTH)

AF:

0.346

AC:

732

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1467

2934

4401

5868

7335

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

510

1020

1530

2040

2550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.227

Hom.:

8116

Bravo

AF:

0.393

Asia WGS

AF:

0.598

AC:

2070

AN:

3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

4.1

(source)

DANN

Benign

0.83

PhyloP100

-0.16

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over