Variant X-153942025-C-T details in Genebe, Genetics Data Aggregator

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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.62

Variant links:

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]

RENBP links:

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ACMG classification

Classification made for transcript

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/exons	MANE	UniProt
RENBP	NM_002910.6 linkuse as main transcript	c.694G>A	p.Gly232Arg	missense_variant	7/11	ENST00000393700.8
RENBP	XM_017029698.2 linkuse as main transcript	c.664G>A	p.Gly222Arg	missense_variant	7/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
RENBP	ENST00000393700.8 linkuse as main transcript	c.694G>A	p.Gly232Arg	missense_variant	7/11	1	NM_002910.6	P1
RENBP	ENST00000369997.7 linkuse as main transcript	c.652G>A	p.Gly218Arg	missense_variant	7/11	5
RENBP	ENST00000423624.5 linkuse as main transcript	c.*515G>A		3_prime_UTR_variant, NMD_transcript_variant	7/11	5
RENBP	ENST00000442361.1 linkuse as main transcript	c.403-372G>A		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.26e-7

AC:

AN:

1080218

Hom.:

Cov.:

AF XY:

0.00000286

AC XY:

AN XY:

349374

show subpopulations

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.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 17, 2024

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

BayesDel_noAF

Uncertain

0.020

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.35

T;.

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.059

MetaRNN

Uncertain

0.70

D;D

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.7

L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.61

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over