Genetic Variant NM_002910.6:c.803G>C (chrX-153941620-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_002910.6(RENBP):c.803G>C(p.Arg268Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,096,424 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. 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. R268H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 19)

Exomes 𝑓: 9.1e-7 ( 0 hom. 1 hem. )

Consequence

RENBP
NM_002910.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.119

Publications

1 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.803G>C	p.Arg268Pro	missense	Exon 8 of 11	NP_002901.2	P51606-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RENBP	ENST00000393700.8	TSL:1 MANE Select	c.803G>C	p.Arg268Pro	missense	Exon 8 of 11	ENSP00000377303.3	P51606-1
RENBP	ENST00000875215.1		c.803G>C	p.Arg268Pro	missense	Exon 8 of 12	ENSP00000545274.1
RENBP	ENST00000369997.7	TSL:5	c.761G>C	p.Arg254Pro	missense	Exon 8 of 11	ENSP00000359014.3	A6NKZ2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000555

AC:

AN:

180269

AF XY:

0.0000153

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000125

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.12e-7

AC:

AN:

1096424

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

362194

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26351

American (AMR)

AF:

0.00

AC:

AN:

35140

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19350

East Asian (EAS)

AF:

0.00

AC:

AN:

30064

South Asian (SAS)

AF:

0.00

AC:

AN:

54005

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39962

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4127

European-Non Finnish (NFE)

AF:

0.00000119

AC:

AN:

841398

Other (OTH)

AF:

0.00

AC:

AN:

46027

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.68

BayesDel_addAF

Benign

-0.0016

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.42

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.78

M_CAP

Benign

0.032

MetaRNN

Uncertain

0.72

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

PhyloP100

0.12

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.6

REVEL

Uncertain

0.33

Sift

Benign

0.044

Sift4G

Benign

0.18

Polyphen

0.99

Vest4

0.65

MutPred

0.60

Loss of catalytic residue at R268 (P = 0.0399)

MVP

0.63

MPC

1.3

ClinPred

0.85

GERP RS

2.4

Varity_R

0.72

gMVP

0.85

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over