Variant rs6644951 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001636.4(SLC25A6):c.599-6G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 1,611,068 control chromosomes in the GnomAD database, including 271,161 homozygotes. There are 463,856 hemizygotes in GnomAD. 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 (no stars).

Frequency

Genomes: 𝑓 0.63 ( 30755 hom., 46852 hem., cov: 33)

Exomes 𝑓: 0.57 ( 240406 hom. 417004 hem. )

Consequence

SLC25A6
NM_001636.4 splice_region, intron

Scores

Splicing: ADA: 0.00002056

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.498

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant X-1387425-C-G is Benign according to our data. Variant chrX-1387425-C-G is described in ClinVar as [Benign]. Clinvar id is 3036192.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A6	NM_001636.4 link	c.599-6G>C		splice_region_variant, intron_variant	Intron 2 of 3	ENST00000381401.11	NP_001627.2	P12236Q6I9V5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC25A6	ENST00000381401.11 link	c.599-6G>C	splice_region_variant, intron_variant	Intron 2 of 3	1	NM_001636.4	ENSP00000370808.5	P12236
SLC25A6	ENST00000475167.6 link	n.792-6G>C	splice_region_variant, intron_variant	Intron 3 of 3	2
SLC25A6	ENST00000484026.6 link	n.780-6G>C	splice_region_variant, intron_variant	Intron 3 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.629

AC:

95559

AN:

151936

Hom.:

30708

Cov.:

AF XY:

0.630

AC XY:

46747

AN XY:

74160

show subpopulations

Gnomad AFR

AF:

0.743

Gnomad AMI

AF:

0.538

Gnomad AMR

AF:

0.675

Gnomad ASJ

AF:

0.694

Gnomad EAS

AF:

0.478

Gnomad SAS

AF:

0.691

Gnomad FIN

AF:

0.592

Gnomad MID

AF:

0.684

Gnomad NFE

AF:

0.559

Gnomad OTH

AF:

0.633

GnomAD3 exomes

AF:

0.610

AC:

151528

AN:

248222

Hom.:

47120

AF XY:

0.612

AC XY:

82355

AN XY:

134512

show subpopulations

Gnomad AFR exome

AF:

0.750

Gnomad AMR exome

AF:

0.672

Gnomad ASJ exome

AF:

0.701

Gnomad EAS exome

AF:

0.471

Gnomad SAS exome

AF:

0.711

Gnomad FIN exome

AF:

0.592

Gnomad NFE exome

AF:

0.562

Gnomad OTH exome

AF:

0.618

GnomAD4 exome

AF:

0.571

AC:

832513

AN:

1459014

Hom.:

240406

Cov.:

AF XY:

0.575

AC XY:

417004

AN XY:

725686

show subpopulations

Gnomad4 AFR exome

AF:

0.753

Gnomad4 AMR exome

AF:

0.674

Gnomad4 ASJ exome

AF:

0.696

Gnomad4 EAS exome

AF:

0.449

Gnomad4 SAS exome

AF:

0.712

Gnomad4 FIN exome

AF:

0.582

Gnomad4 NFE exome

AF:

0.550

Gnomad4 OTH exome

AF:

0.588

GnomAD4 genome

AF:

0.629

AC:

95660

AN:

152054

Hom.:

30755

Cov.:

AF XY:

0.631

AC XY:

46852

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.743

Gnomad4 AMR

AF:

0.675

Gnomad4 ASJ

AF:

0.694

Gnomad4 EAS

AF:

0.477

Gnomad4 SAS

AF:

0.692

Gnomad4 FIN

AF:

0.592

Gnomad4 NFE

AF:

0.559

Gnomad4 OTH

AF:

0.629

Bravo

AF:

0.637

EpiCase

AF:

0.574

EpiControl

AF:

0.570

ClinVar

Significance: 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: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as 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

-0.80

CADD

Benign

0.98

DANN

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000021

dbscSNV1_RF

Benign

0.0

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