17-8288847-T-G

Variant names:

• chr17-8288847-T-G
• rs900647124
• NM_016492.5:c.59T>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016492.5(RANGRF):​c.59T>G​(p.Met20Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RANGRF NM_016492.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0440

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04256159).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RANGRF	NM_016492.5	c.59T>G	p.Met20Arg	missense_variant	Exon 1 of 5	ENST00000226105.11	NP_057576.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RANGRF	ENST00000226105.11	c.59T>G	p.Met20Arg	missense_variant	Exon 1 of 5	1	NM_016492.5	ENSP00000226105.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	12
DANN	Benign	0.70
DEOGEN2	Benign	0.018	T;.;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.033	T;T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.043	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.3	N;N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.14	N;N;.;N
REVEL	Benign	0.11
Sift	Benign	0.29	T;T;.;T
Sift4G	Benign	0.46	T;T;T;T
Polyphen		0.0	B;.;B;B
Vest4		0.14
MutPred		0.35		Gain of methylation at M20 (P = 0.0602);Gain of methylation at M20 (P = 0.0602);Gain of methylation at M20 (P = 0.0602);Gain of methylation at M20 (P = 0.0602);
MVP		0.21
MPC		0.32
ClinPred		0.056	T
GERP RS		0.97
Varity_R		0.25
gMVP		0.40

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: rs900647124; hg19: chr17-8192165;