X-153942913-G-T

Variant names:

• chrX-153942913-G-T
• rs142718878
• NM_002910.6:c.629C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_002910.6(RENBP):​c.629C>A​(p.Ala210Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 24)
• Consequence: RENBP NM_002910.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.35

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM1: In a mutagenesis_site Activity is similiar to wild-type. (size 0) in uniprot entity RENBP_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16353244).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RENBP	NM_002910.6	c.629C>A	p.Ala210Glu	missense_variant	Exon 6 of 11	ENST00000393700.8	NP_002901.2
RENBP	XM_017029698.2	c.599C>A	p.Ala200Glu	missense_variant	Exon 6 of 11		XP_016885187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RENBP	ENST00000393700.8	c.629C>A	p.Ala210Glu	missense_variant	Exon 6 of 11	1	NM_002910.6	ENSP00000377303.3

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.25	T;.
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.60	T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.16
Sift	Benign	0.77	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.89	P;.
Vest4		0.37
MutPred		0.53		Gain of disorder (P = 0.0431);.;
MVP		0.26
MPC		0.93
ClinPred		0.33	T
GERP RS		2.1
Varity_R		0.20
gMVP		0.61

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

Other links and lift over

dbSNP: rs142718878; hg19: chrX-153208365;