X-153942025-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002910.6. 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
	RENBP	NM_002910.6	MANE Select	c.694G>A	p.Gly232Arg	missense	Exon 7 of 11	NP_002901.2	P51606-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RENBP	ENST00000393700.8	TSL:1 MANE Select	c.694G>A	p.Gly232Arg	missense	Exon 7 of 11	ENSP00000377303.3	P51606-1
	RENBP	ENST00000875215.1		c.694G>A	p.Gly232Arg	missense	Exon 7 of 12	ENSP00000545274.1
	RENBP	ENST00000369997.7	TSL:5	c.652G>A	p.Gly218Arg	missense	Exon 7 of 11	ENSP00000359014.3	A6NKZ2

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

African (AFR) AF: 0.00 AC: 0 AN: 25941

American (AMR) AF: 0.00 AC: 0 AN: 34738

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18933

East Asian (EAS) AF: 0.00 AC: 0 AN: 29361

South Asian (SAS) AF: 0.00 AC: 0 AN: 53859

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39050

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4051

European-Non Finnish (NFE) AF: 0.00000121 AC: 1 AN: 829207

Other (OTH) AF: 0.00 AC: 0 AN: 45078

GnomAD4 genome Cov.: 20

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.059	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.7	L
PhyloP100		3.6
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.44
Sift	Benign	0.12	T
Sift4G	Benign	0.39	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
Mutation Taster		=29/71	disease causing

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

Other links and lift over

dbSNP: rs2065229226; hg19: chrX-153207478;