17-8288633-A-G

Position:

• chr17-8288633-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.269

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]

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
RANGRF	NM_016492.5			upstream_gene_variant		ENST00000226105.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RANGRF	ENST00000226105.11			upstream_gene_variant		1	NM_016492.5	P1

Frequencies

GnomAD3 genomes AF: 0.0333 AC: 5063 AN: 152184 Hom.: 134 Cov.: 32

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.: 9 AF XY: 0.0204 AC XY: 7681 AN XY: 376354

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.: 32 AF XY: 0.0336 AC XY: 2505 AN XY: 74482

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.: 19

Bravo AF: 0.0346

Asia WGS AF: 0.0560 AC: 193 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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

Other links and lift over

dbSNP: rs113617815; hg19: chr17-8191951; COSMIC: COSV56839640; COSMIC: COSV56839640;