rs35420920

Variant names:

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_016492.5(RANGRF):c.510G>A(p.Gln170Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00223 in 1,614,180 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 8 hom. )

Consequence

RANGRF
NM_016492.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.422

Variant links:

Genes affected

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:

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 17-8289885-G-A is Benign according to our data. Variant chr17-8289885-G-A is described in ClinVar as [Benign]. Clinvar id is 138889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-8289885-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.422 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RANGRF	NM_016492.5 link	c.510G>A	p.Gln170Gln	synonymous_variant	Exon 5 of 5	ENST00000226105.11	NP_057576.2	Q9HD47-1
SLC25A35	NM_001320870.2 link	c.*620C>T		downstream_gene_variant		ENST00000577745.2	NP_001307799.1	Q3KQZ1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RANGRF	ENST00000226105.11 link	c.510G>A	p.Gln170Gln	synonymous_variant	Exon 5 of 5	1	NM_016492.5	ENSP00000226105.6		Q9HD47-1
SLC25A35	ENST00000577745.2 link	c.*620C>T		downstream_gene_variant		1	NM_001320870.2	ENSP00000464231.1		Q3KQZ1-1

Frequencies

GnomAD3 genomes

AF:

0.00224

AC:

341

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00509

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00370

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00218

AC:

549

AN:

251484

Hom.:

AF XY:

0.00208

AC XY:

283

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00198

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000490

Gnomad FIN exome

AF:

0.00550

Gnomad NFE exome

AF:

0.00326

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00222

AC:

3251

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00226

AC XY:

1642

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.00149

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000545

Gnomad4 FIN exome

AF:

0.00474

Gnomad4 NFE exome

AF:

0.00251

Gnomad4 OTH exome

AF:

0.00159

GnomAD4 genome

AF:

0.00224

AC:

341

AN:

152300

Hom.:

Cov.:

AF XY:

0.00218

AC XY:

162

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00509

Gnomad4 NFE

AF:

0.00370

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00295

Hom.:

Bravo

AF:

0.00127

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00240

EpiControl

AF:

0.00184

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jun 03, 2014

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Apr 14, 2024

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Cardiac arrhythmia

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

5.0

DANN

Benign

0.71

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