Variant chr17-8288633-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000579192.5(SLC25A35):c.*43-201T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0224 in 865,558 control chromosomes in the GnomAD database, including 352 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 139 hom., cov: 32)

Exomes 𝑓: 0.020 ( 213 hom. )

Consequence

SLC25A35
ENST00000579192.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.269

Variant links:

Genes affected

SLC25A35 (HGNC:31921): (solute carrier family 25 member 35) SLC25A35 belongs to the SLC25 family of mitochondrial carrier proteins (Haitina et al., 2006 [PubMed 16949250]).[supplied by OMIM, Mar 2008]

SLC25A35 links:

SLC25A35 (HGNC:):

SLC25A35 links:

RANGRF (HGNC:17679): (RAN guanine nucleotide release factor) This gene encodes a protein that has been shown to function as a guanine nucleotide release factor in mouse and to regulate the expression and function of the Nav1.5 cardiac sodium channel in human. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2010]

RANGRF links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 17-8288633-A-G is Benign according to our data. Variant chr17-8288633-A-G is described in ClinVar as [Benign]. Clinvar id is 1292115.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RANGRF	NM_016492.5 linkuse as main transcript	c.-156A>G		upstream_gene_variant		ENST00000226105.11	NP_057576.2	Q9HD47-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RANGRF	ENST00000226105.11 linkuse as main transcript	c.-156A>G		upstream_gene_variant		1	NM_016492.5	ENSP00000226105.6		Q9HD47-1

Frequencies

GnomAD3 genomes

AF:

0.0333

AC:

5063

AN:

152184

Hom.:

134

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0691

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0241

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.00347

Gnomad SAS

AF:

0.0364

Gnomad FIN

AF:

0.0250

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0186

Gnomad OTH

AF:

0.0229

GnomAD4 exome

AF:

0.0200

AC:

14255

AN:

713256

Hom.:

213

Cov.:

AF XY:

0.0204

AC XY:

7681

AN XY:

376354

show subpopulations

Gnomad4 AFR exome

AF:

0.0704

Gnomad4 AMR exome

AF:

0.0150

Gnomad4 ASJ exome

AF:

0.0119

Gnomad4 EAS exome

AF:

0.00133

Gnomad4 SAS exome

AF:

0.0359

Gnomad4 FIN exome

AF:

0.0209

Gnomad4 NFE exome

AF:

0.0172

Gnomad4 OTH exome

AF:

0.0235

GnomAD4 genome

AF:

0.0335

AC:

5101

AN:

152302

Hom.:

139

Cov.:

AF XY:

0.0336

AC XY:

2505

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0698

Gnomad4 AMR

AF:

0.0240

Gnomad4 ASJ

AF:

0.0138

Gnomad4 EAS

AF:

0.00348

Gnomad4 SAS

AF:

0.0367

Gnomad4 FIN

AF:

0.0250

Gnomad4 NFE

AF:

0.0186

Gnomad4 OTH

AF:

0.0232

Alfa

AF:

0.0277

Hom.:

Bravo

AF:

0.0346

Asia WGS

AF:

0.0560

AC:

193

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 27, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

7.1

DANN

Benign

0.52

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