Variant X-153935374-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002910.6(RENBP):c.1196T>C(p.Met399Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000531 in 1,128,918 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.0000049 ( 0 hom. 1 hem. )

Consequence

RENBP
NM_002910.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.96

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 made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33305866).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RENBP	NM_002910.6 link	c.1196T>C	p.Met399Thr	missense_variant	Exon 11 of 11	ENST00000393700.8	NP_002901.2	P51606
RENBP	XM_017029698.2 link	c.1166T>C	p.Met389Thr	missense_variant	Exon 11 of 11		XP_016885187.1	P51606-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RENBP	ENST00000393700.8 link	c.1196T>C	p.Met399Thr	missense_variant	Exon 11 of 11	1	NM_002910.6	ENSP00000377303.3		P51606

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111620

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33876

show subpopulations

Gnomad AFR

AF:

0.0000324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000363

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000187

AC:

AN:

106983

Hom.:

AF XY:

0.00

AC XY:

AN XY:

30213

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 SAS exome

AF:

0.000249

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000492

AC:

AN:

1017251

Hom.:

Cov.:

AF XY:

0.00000312

AC XY:

AN XY:

320793

show subpopulations

Gnomad4 AFR exome

AF:

0.0000429

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000683

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000125

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000896

AC:

AN:

111667

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33933

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000364

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 23, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1196T>C (p.M399T) alteration is located in exon 11 (coding exon 11) of the RENBP gene. This alteration results from a T to C substitution at nucleotide position 1196, causing the methionine (M) at amino acid position 399 to be replaced by a threonine (T). 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

0.34

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.49

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.50

D;.;T

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.84

T;T;T

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.33

T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.1

L;.;.

PrimateAI

Pathogenic

0.92

PROVEAN

Uncertain

-3.9

D;D;D

REVEL

Benign

0.29

Sift

Benign

0.064

T;T;D

Sift4G

Uncertain

0.0090

D;D;.

Polyphen

1.0

D;.;.

Vest4

0.57

MutPred

0.39

Gain of glycosylation at M399 (P = 0.0252);.;.;

MVP

0.30

MPC

0.75

ClinPred

0.58

GERP RS

4.1

Varity_R

0.73

gMVP

0.67

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

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