Variant rs143216483 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_001636.4(SLC25A6):c.429G>A(p.Ala143Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0034 in 1,613,714 control chromosomes in the GnomAD database, including 14 homozygotes. There are 2,624 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 0 hom., 171 hem., cov: 32)

Exomes 𝑓: 0.0035 ( 14 hom. 2453 hem. )

Consequence

SLC25A6
NM_001636.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.191

Variant links:

Genes affected

SLC25A6 (HGNC:10992): (solute carrier family 25 member 6) This gene is a member of the mitochondrial carrier subfamily of solute carrier protein genes. The product of this gene functions as a gated pore that translocates ADP from the cytoplasm into the mitochondrial matrix and ATP from the mitochondrial matrix into the cytoplasm. The protein is implicated in the function of the permability transition pore complex (PTPC), which regulates the release of mitochondrial products that induce apoptosis. The human genome contains several non-transcribed pseudogenes of this gene. [provided by RefSeq, Jun 2013]

SLC25A6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant X-1389410-C-T is Benign according to our data. Variant chrX-1389410-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 788322.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.191 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 171 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A6	NM_001636.4 link	c.429G>A	p.Ala143Ala	synonymous_variant	Exon 2 of 4	ENST00000381401.11	NP_001627.2	P12236Q6I9V5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC25A6	ENST00000381401.11 link	c.429G>A	p.Ala143Ala	synonymous_variant	Exon 2 of 4	1	NM_001636.4	ENSP00000370808.5	P12236
SLC25A6	ENST00000475167.6 link	n.622G>A		non_coding_transcript_exon_variant	Exon 3 of 4	2
SLC25A6	ENST00000484026.6 link	n.610G>A		non_coding_transcript_exon_variant	Exon 3 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.00231

AC:

351

AN:

152200

Hom.:

Cov.:

AF XY:

0.00230

AC XY:

171

AN XY:

74340

show subpopulations

Gnomad AFR

AF:

0.000506

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00465

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00345

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00190

AC:

476

AN:

251174

Hom.:

AF XY:

0.00194

AC XY:

263

AN XY:

135754

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00231

Gnomad ASJ exome

AF:

0.00327

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00302

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00352

AC:

5137

AN:

1461396

Hom.:

Cov.:

AF XY:

0.00337

AC XY:

2453

AN XY:

726984

show subpopulations

Gnomad4 AFR exome

AF:

0.000359

Gnomad4 AMR exome

AF:

0.00219

Gnomad4 ASJ exome

AF:

0.00321

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.000543

Gnomad4 NFE exome

AF:

0.00425

Gnomad4 OTH exome

AF:

0.00300

GnomAD4 genome

AF:

0.00230

AC:

351

AN:

152318

Hom.:

Cov.:

AF XY:

0.00230

AC XY:

171

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.00464

Gnomad4 ASJ

AF:

0.00375

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00345

Gnomad4 OTH

AF:

0.00237

Bravo

AF:

0.00218

EpiCase

AF:

0.00409

EpiControl

AF:

0.00267

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

1.6

DANN

Benign

0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.4

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over