17-8288802-G-C

Variant names:

• chr17-8288802-G-C
• rs1990238766
• NM_016492.5:c.14G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016492.5(RANGRF):​c.14G>C​(p.Arg5Thr) 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. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R5K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RANGRF NM_016492.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.487
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.081888676).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RANGRF	NM_016492.5	MANE Select	c.14G>C	p.Arg5Thr	missense	Exon 1 of 5	NP_057576.2
	RANGRF	NM_001177802.2		c.14G>C	p.Arg5Thr	missense	Exon 1 of 3	NP_001171273.1	Q9HD47-3
	RANGRF	NM_001177801.2		c.14G>C	p.Arg5Thr	missense	Exon 1 of 4	NP_001171272.1	Q9HD47-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RANGRF	ENST00000226105.11	TSL:1 MANE Select	c.14G>C	p.Arg5Thr	missense	Exon 1 of 5	ENSP00000226105.6	Q9HD47-1
	RANGRF	ENST00000439238.3	TSL:1	c.14G>C	p.Arg5Thr	missense	Exon 1 of 3	ENSP00000413190.3	Q9HD47-3
	RANGRF	ENST00000407006.8	TSL:1	c.14G>C	p.Arg5Thr	missense	Exon 1 of 4	ENSP00000383940.4	Q9HD47-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	12
DANN	Benign	0.60
DEOGEN2	Benign	0.020	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.025	N
PhyloP100		0.49
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.13
Sift	Benign	0.066	T
Sift4G	Benign	0.18	T
Polyphen		0.0010	B
Vest4		0.24
MutPred		0.34		Gain of glycosylation at R5 (P = 0.0288)
MVP		0.32
MPC		0.32
ClinPred		0.098	T
GERP RS		2.3
PromoterAI		-0.049	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.066
gMVP		0.50

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: rs1990238766; hg19: chr17-8192120;