rs782242143

Variant names:

• chrX-153943898-C-A
• rs782242143
• NM_002910.6:c.286G>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002910.6(RENBP):​c.286G>T​(p.Ala96Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000079 in 1,177,628 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 39 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 0.00031 (0 hom., 19 hem., cov: 24)
  • Exomes 𝑓: 0.000054 (0 hom. 20 hem.)
• Consequence: RENBP NM_002910.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.02
• Publications: 1 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.063818544).
• BS2: High Hemizygotes in GnomAd4 at 19 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.286G>T	p.Ala96Ser	missense	Exon 4 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.286G>T	p.Ala96Ser	missense	Exon 4 of 11	ENSP00000377303.3	P51606-1
	RENBP	ENST00000875215.1		c.286G>T	p.Ala96Ser	missense	Exon 4 of 12	ENSP00000545274.1
	RENBP	ENST00000369997.7	TSL:5	c.244G>T	p.Ala82Ser	missense	Exon 4 of 11	ENSP00000359014.3	A6NKZ2

Frequencies

GnomAD3 genomes AF: 0.000310 AC: 35 AN: 113023 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00297

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000562

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000180 AC: 23 AN: 127472 AF XY: 0.000167

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000912

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000778

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000545 AC: 58 AN: 1064605 Hom.: 0 Cov.: 32 AF XY: 0.0000576 AC XY: 20 AN XY: 347167

African (AFR) AF: 0.00 AC: 0 AN: 25416

American (AMR) AF: 0.000648 AC: 19 AN: 29308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18812

East Asian (EAS) AF: 0.00 AC: 0 AN: 27893

South Asian (SAS) AF: 0.00 AC: 0 AN: 51108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38057

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4099

European-Non Finnish (NFE) AF: 0.0000388 AC: 32 AN: 825075

Other (OTH) AF: 0.000156 AC: 7 AN: 44837

GnomAD4 genome AF: 0.000310 AC: 35 AN: 113023 Hom.: 0 Cov.: 24 AF XY: 0.000540 AC XY: 19 AN XY: 35157

African (AFR) AF: 0.00 AC: 0 AN: 31132

American (AMR) AF: 0.00297 AC: 32 AN: 10757

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2664

East Asian (EAS) AF: 0.00 AC: 0 AN: 3587

South Asian (SAS) AF: 0.00 AC: 0 AN: 2806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.0000562 AC: 3 AN: 53336

Other (OTH) AF: 0.00 AC: 0 AN: 1522

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000280

ExAC AF: 0.0000263 AC: 3

ClinVar

ClinVar submissions as Germline

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	0.10
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.15	T
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.45	N
PhyloP100		3.0
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.064
Sift	Benign	0.87	T
Sift4G	Benign	0.75	T
Polyphen		0.17	B
Vest4		0.23
MVP		0.29
MPC		0.43
ClinPred		0.034	T
GERP RS		4.8
Varity_R		0.23
gMVP		0.59
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs782242143; hg19: chrX-153209350;