Variant 17-8288620-C-T 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.*43-188G>A 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 775,368 control chromosomes in the GnomAD database, including 324 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 129 hom., cov: 32)

Exomes 𝑓: 0.020 ( 195 hom. )

Consequence

SLC25A35
ENST00000579192.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.02

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:

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=-0.68).

BP6

Variant 17-8288620-C-T is Benign according to our data. Variant chr17-8288620-C-T is described in ClinVar as [Benign]. Clinvar id is 1224078.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0634 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			upstream_gene_variant		ENST00000226105.11	NP_057576.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RANGRF	ENST00000226105.11 linkuse as main transcript			upstream_gene_variant		1	NM_016492.5	ENSP00000226105	P1	Q9HD47-1

Frequencies

GnomAD3 genomes

AF:

0.0321

AC:

4883

AN:

152160

Hom.:

127

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0649

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0236

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.00347

Gnomad SAS

AF:

0.0367

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:

12462

AN:

623090

Hom.:

195

Cov.:

AF XY:

0.0204

AC XY:

6759

AN XY:

331538

show subpopulations

Gnomad4 AFR exome

AF:

0.0659

Gnomad4 AMR exome

AF:

0.0148

Gnomad4 ASJ exome

AF:

0.0120

Gnomad4 EAS exome

AF:

0.00130

Gnomad4 SAS exome

AF:

0.0359

Gnomad4 FIN exome

AF:

0.0208

Gnomad4 NFE exome

AF:

0.0173

Gnomad4 OTH exome

AF:

0.0231

GnomAD4 genome

AF:

0.0323

AC:

4911

AN:

152278

Hom.:

129

Cov.:

AF XY:

0.0325

AC XY:

2421

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0654

Gnomad4 AMR

AF:

0.0235

Gnomad4 ASJ

AF:

0.0138

Gnomad4 EAS

AF:

0.00347

Gnomad4 SAS

AF:

0.0369

Gnomad4 FIN

AF:

0.0250

Gnomad4 NFE

AF:

0.0186

Gnomad4 OTH

AF:

0.0232

Alfa

AF:

0.0262

Hom.:

Bravo

AF:

0.0333

Asia WGS

AF:

0.0540

AC:

188

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

-0.68

CADD

Benign

DANN

Benign

0.79

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