Variant rs6644950 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001636.4(SLC25A6):c.687C>T(p.Tyr229Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0141 in 1,613,348 control chromosomes in the GnomAD database, including 481 homozygotes. There are 11,322 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.012 ( 44 hom., 929 hem., cov: 33)

Exomes 𝑓: 0.014 ( 437 hom. 10393 hem. )

Consequence

SLC25A6
NM_001636.4 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.54

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant X-1387331-G-A is Benign according to our data. Variant chrX-1387331-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3032859.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=2.54 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A6	NM_001636.4 link	c.687C>T	p.Tyr229Tyr	synonymous_variant	Exon 3 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.687C>T	p.Tyr229Tyr	synonymous_variant	Exon 3 of 4	1	NM_001636.4	ENSP00000370808.5	P12236
SLC25A6	ENST00000475167.6 link	n.880C>T		non_coding_transcript_exon_variant	Exon 4 of 4	2
SLC25A6	ENST00000484026.6 link	n.*14C>T		downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0122

AC:

1850

AN:

152194

Hom.:

Cov.:

AF XY:

0.0125

AC XY:

929

AN XY:

74340

show subpopulations

Gnomad AFR

AF:

0.00183

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.00380

Gnomad ASJ

AF:

0.0170

Gnomad EAS

AF:

0.122

Gnomad SAS

AF:

0.0149

Gnomad FIN

AF:

0.0130

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0113

Gnomad OTH

AF:

0.00955

GnomAD3 exomes

AF:

0.0193

AC:

4843

AN:

250462

Hom.:

173

AF XY:

0.0196

AC XY:

2657

AN XY:

135502

show subpopulations

Gnomad AFR exome

AF:

0.00154

Gnomad AMR exome

AF:

0.00333

Gnomad ASJ exome

AF:

0.0159

Gnomad EAS exome

AF:

0.128

Gnomad SAS exome

AF:

0.0163

Gnomad FIN exome

AF:

0.0170

Gnomad NFE exome

AF:

0.0110

Gnomad OTH exome

AF:

0.0136

GnomAD4 exome

AF:

0.0143

AC:

20841

AN:

1461036

Hom.:

437

Cov.:

AF XY:

0.0143

AC XY:

10393

AN XY:

726850

show subpopulations

Gnomad4 AFR exome

AF:

0.00155

Gnomad4 AMR exome

AF:

0.00315

Gnomad4 ASJ exome

AF:

0.0182

Gnomad4 EAS exome

AF:

0.116

Gnomad4 SAS exome

AF:

0.0156

Gnomad4 FIN exome

AF:

0.0163

Gnomad4 NFE exome

AF:

0.0112

Gnomad4 OTH exome

AF:

0.0140

GnomAD4 genome

AF:

0.0122

AC:

1852

AN:

152312

Hom.:

Cov.:

AF XY:

0.0125

AC XY:

929

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00183

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.0170

Gnomad4 EAS

AF:

0.122

Gnomad4 SAS

AF:

0.0152

Gnomad4 FIN

AF:

0.0130

Gnomad4 NFE

AF:

0.0113

Gnomad4 OTH

AF:

0.0113

Bravo

AF:

0.0119

EpiCase

AF:

0.00911

EpiControl

AF:

0.0108

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SLC25A6-related disorder

Benign:1

Feb 16, 2021

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

1.4

DANN

Uncertain

0.98

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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