Genetic Variant RENBP:p.Ala172Thr (chrX-153943028-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002910.6(RENBP):c.514G>A(p.Ala172Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000141 in 1,201,690 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000088 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000015 ( 0 hom. 5 hem. )

Consequence

RENBP
NM_002910.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.72

Publications

2 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: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.060406297).

BS2

High Hemizygotes in GnomAdExome4 at 5 gene

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.514G>A	p.Ala172Thr	missense	Exon 6 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.514G>A	p.Ala172Thr	missense	Exon 6 of 11	ENSP00000377303.3	P51606-1
RENBP	ENST00000875215.1		c.514G>A	p.Ala172Thr	missense	Exon 6 of 12	ENSP00000545274.1
RENBP	ENST00000369997.7	TSL:5	c.472G>A	p.Ala158Thr	missense	Exon 6 of 11	ENSP00000359014.3	A6NKZ2

Frequencies

GnomAD3 genomes

AF:

0.00000884

AC:

AN:

113177

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000278

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000238

AC:

AN:

168142

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000301

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000147

AC:

AN:

1088513

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

356115

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26238

American (AMR)

AF:

0.00

AC:

AN:

34579

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18844

East Asian (EAS)

AF:

0.000200

AC:

AN:

30059

South Asian (SAS)

AF:

0.00

AC:

AN:

52912

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39055

Middle Eastern (MID)

AF:

0.000273

AC:

AN:

3666

European-Non Finnish (NFE)

AF:

0.0000107

AC:

AN:

837500

Other (OTH)

AF:

0.00

AC:

AN:

45660

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000884

AC:

AN:

113177

Hom.:

Cov.:

AF XY:

0.0000283

AC XY:

AN XY:

35333

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31184

American (AMR)

AF:

0.00

AC:

AN:

10842

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2654

East Asian (EAS)

AF:

0.000278

AC:

AN:

3598

South Asian (SAS)

AF:

0.00

AC:

AN:

2819

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6334

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53284

Other (OTH)

AF:

0.00

AC:

AN:

1534

Age Distribution

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000828

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.93

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.17

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.85

M_CAP

Benign

0.0097

MetaRNN

Benign

0.060

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.49

PhyloP100

1.7

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.080

REVEL

Benign

0.017

Sift

Benign

0.12

Sift4G

Benign

0.29

Polyphen

0.0060

Vest4

0.098

MutPred

0.31

Loss of helix (P = 0.028)

MVP

0.14

MPC

0.38

ClinPred

0.087

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.048

gMVP

0.45

Mutation Taster

=98/2

polymorphism

(source)

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

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over