Variant NM_001636.4:c.762C>T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001636.4(SLC25A6):c.762C>T(p.Thr254Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00322 in 1,610,794 control chromosomes in the GnomAD database, including 10 homozygotes. There are 2,498 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 0.0022 ( 1 hom., 151 hem., cov: 32)

Exomes 𝑓: 0.0033 ( 9 hom. 2347 hem. )

Consequence

SLC25A6
NM_001636.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.404

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant X-1386737-G-A is Benign according to our data. Variant chrX-1386737-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 774972.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.404 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 151 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A6	NM_001636.4 link	c.762C>T	p.Thr254Thr	synonymous_variant	Exon 4 of 4	ENST00000381401.11	NP_001627.2	P12236Q6I9V5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A6	ENST00000381401.11 link	c.762C>T	p.Thr254Thr	synonymous_variant	Exon 4 of 4	1	NM_001636.4	ENSP00000370808.5		P12236

Frequencies

GnomAD3 genomes

AF:

0.00220

AC:

335

AN:

152018

Hom.:

Cov.:

AF XY:

0.00203

AC XY:

151

AN XY:

74238

show subpopulations

Gnomad AFR

AF:

0.000846

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00123

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00372

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.00218

AC:

541

AN:

248074

Hom.:

AF XY:

0.00230

AC XY:

308

AN XY:

134102

show subpopulations

Gnomad AFR exome

AF:

0.000743

Gnomad AMR exome

AF:

0.00100

Gnomad ASJ exome

AF:

0.000908

Gnomad EAS exome

AF:

0.0000554

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00227

Gnomad NFE exome

AF:

0.00371

Gnomad OTH exome

AF:

0.00333

GnomAD4 exome

AF:

0.00333

AC:

4852

AN:

1458658

Hom.:

Cov.:

AF XY:

0.00323

AC XY:

2347

AN XY:

725592

show subpopulations

Gnomad4 AFR exome

AF:

0.000540

Gnomad4 AMR exome

AF:

0.000970

Gnomad4 ASJ exome

AF:

0.00131

Gnomad4 EAS exome

AF:

0.0000759

Gnomad4 SAS exome

AF:

0.0000582

Gnomad4 FIN exome

AF:

0.00244

Gnomad4 NFE exome

AF:

0.00402

Gnomad4 OTH exome

AF:

0.00261

GnomAD4 genome

AF:

0.00220

AC:

335

AN:

152136

Hom.:

Cov.:

AF XY:

0.00203

AC XY:

151

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.000843

Gnomad4 AMR

AF:

0.00177

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00123

Gnomad4 NFE

AF:

0.00372

Gnomad4 OTH

AF:

0.000948

Bravo

AF:

0.00211

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

0.64

DANN

Benign

0.95

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