rs138959557

Variant names:

• chr17-8289331-T-C
• rs138959557
• NM_016492.5:c.268T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-8289331-T-C
• chr17-8289331-T-G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_016492.5(RANGRF):​c.268T>C​(p.Leu90Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000589 in 1,614,148 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0032 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00032 (2 hom.)
• Consequence: RANGRF NM_016492.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.145
• Publications: 0 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 17-8289331-T-C is Benign according to our data. Variant chr17-8289331-T-C is described in ClinVar as Benign. ClinVar VariationId is 285529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.145 with no splicing effect.
• BS2: High AC in GnomAd4 at 482 Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016492.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RANGRF	NM_016492.5	MANE Select	c.268T>C	p.Leu90Leu	synonymous	Exon 3 of 5	NP_057576.2
	RANGRF	NM_001177802.2		c.268T>C	p.Leu90Leu	synonymous	Exon 3 of 3	NP_001171273.1
	RANGRF	NM_001177801.2		c.268T>C	p.Leu90Leu	synonymous	Exon 3 of 4	NP_001171272.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RANGRF	ENST00000226105.11	TSL:1 MANE Select	c.268T>C	p.Leu90Leu	synonymous	Exon 3 of 5	ENSP00000226105.6
	RANGRF	ENST00000439238.3	TSL:1	c.268T>C	p.Leu90Leu	synonymous	Exon 3 of 3	ENSP00000413190.3
	RANGRF	ENST00000407006.8	TSL:1	c.268T>C	p.Leu90Leu	synonymous	Exon 3 of 4	ENSP00000383940.4

Frequencies

GnomAD3 genomes AF: 0.00314 AC: 477 AN: 152150 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0112

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00192

GnomAD2 exomes AF: 0.000764 AC: 192 AN: 251444 AF XY: 0.000640

Gnomad AFR exome AF: 0.0108

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000320 AC: 468 AN: 1461880 Hom.: 2 Cov.: 31 AF XY: 0.000268 AC XY: 195 AN XY: 727240

African (AFR) AF: 0.0122 AC: 407 AN: 33480

American (AMR) AF: 0.000335 AC: 15 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5762

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112010

Other (OTH) AF: 0.000662 AC: 40 AN: 60392

GnomAD4 genome AF: 0.00317 AC: 482 AN: 152268 Hom.: 1 Cov.: 32 AF XY: 0.00310 AC XY: 231 AN XY: 74438

African (AFR) AF: 0.0112 AC: 467 AN: 41550

American (AMR) AF: 0.000589 AC: 9 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68018

Other (OTH) AF: 0.00190 AC: 4 AN: 2110

Alfa AF: 0.00150 Hom.: 1

Bravo AF: 0.00332

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Cardiac arrhythmia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.5
DANN	Benign	0.79
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs138959557; hg19: chr17-8192649;