X-153942025-C-T

Variant names:

• chrX-153942025-C-T
• rs2065229226
• NM_002910.6:c.694G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002910.6(RENBP):​c.694G>A​(p.Gly232Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000926 in 1,080,218 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 9.3e-7 (0 hom. 1 hem.)
• Consequence: RENBP NM_002910.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.62

Genes affected

RENBP (HGNC:9959): (renin binding protein) The gene product inhibits renin activity by forming a dimer with renin, a complex known as high molecular weight renin. The encoded protein contains a leucine zipper domain, which is essential for its dimerization with renin. The gene product can catalyze the interconversion of N-acetylglucosamine to N-acetylmannosamine, indicating that it is a GlcNAc 2-epimerase. Transcript variants utilizing alternative promoters have been described in the literature. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RENBP	NM_002910.6	c.694G>A	p.Gly232Arg	missense_variant	Exon 7 of 11	ENST00000393700.8	NP_002901.2
RENBP	XM_017029698.2	c.664G>A	p.Gly222Arg	missense_variant	Exon 7 of 11		XP_016885187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RENBP	ENST00000393700.8	c.694G>A	p.Gly232Arg	missense_variant	Exon 7 of 11	1	NM_002910.6	ENSP00000377303.3

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome AF: 9.26e-7 AC: 1 AN: 1080218 Hom.: 0 Cov.: 30 AF XY: 0.00000286 AC XY: 1 AN XY: 349374

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000121

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 20

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 17, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.694G>A (p.G232R) alteration is located in exon 7 (coding exon 7) of the RENBP gene. This alteration results from a G to A substitution at nucleotide position 694, causing the glycine (G) at amino acid position 232 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Benign	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.35	T;.
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.059	D
MetaRNN	Uncertain	0.70	D;D
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.7	L;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.9	D;D
REVEL	Uncertain	0.44
Sift	Benign	0.12	T;D
Sift4G	Benign	0.39	T;T
Polyphen		1.0	D;.
Vest4		0.43
MutPred		0.79		Gain of solvent accessibility (P = 0.0055);.;
MVP		0.56
MPC		1.2
ClinPred		0.99	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.53
gMVP		0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs2065229226; hg19: chrX-153207478;