Variant rs3809740 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_016492.5(RANGRF):c.81C>T(p.Asp27Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00255 in 1,614,174 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0035 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 36 hom. )

Consequence

RANGRF
NM_016492.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.246

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:

RANGRF (HGNC:):

RANGRF links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 17-8288959-C-T is Benign according to our data. Variant chr17-8288959-C-T is described in ClinVar as [Benign]. Clinvar id is 241109.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-8288959-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.246 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00245 (3585/1461826) while in subpopulation EAS AF= 0.0166 (660/39700). AF 95% confidence interval is 0.0156. There are 36 homozygotes in gnomad4_exome. There are 1776 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RANGRF	NM_016492.5 linkuse as main transcript	c.81C>T	p.Asp27Asp	synonymous_variant	2/5	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.81C>T	p.Asp27Asp	synonymous_variant	2/5	1	NM_016492.5	ENSP00000226105.6		Q9HD47-1

Frequencies

GnomAD3 genomes

AF:

0.00346

AC:

526

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.0143

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.0277

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00184

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00444

AC:

1115

AN:

251044

Hom.:

AF XY:

0.00443

AC XY:

602

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.000186

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00477

Gnomad EAS exome

AF:

0.0146

Gnomad SAS exome

AF:

0.00235

Gnomad FIN exome

AF:

0.0262

Gnomad NFE exome

AF:

0.00123

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00245

AC:

3585

AN:

1461826

Hom.:

Cov.:

AF XY:

0.00244

AC XY:

1776

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00429

Gnomad4 EAS exome

AF:

0.0166

Gnomad4 SAS exome

AF:

0.00220

Gnomad4 FIN exome

AF:

0.0265

Gnomad4 NFE exome

AF:

0.000934

Gnomad4 OTH exome

AF:

0.00258

GnomAD4 genome

AF:

0.00345

AC:

526

AN:

152348

Hom.:

Cov.:

AF XY:

0.00462

AC XY:

344

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00432

Gnomad4 EAS

AF:

0.0145

Gnomad4 SAS

AF:

0.00165

Gnomad4 FIN

AF:

0.0277

Gnomad4 NFE

AF:

0.00184

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00138

Hom.:

Bravo

AF:

0.00120

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.000818

EpiControl

AF:

0.00107

ClinVar

Significance: Benign

Submissions summary: Benign:4

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	Mar 03, 2015	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

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

Apr 28, 2024

- -

Cardiac arrhythmia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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