X-153943078-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002910.6(RENBP):c.464C>T(p.Thr155Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,031,925 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.000012 (0 hom. 4 hem.)
• Consequence: RENBP NM_002910.6 missense, splice_region
• Scores: Splicing: ADA: 0.00007311
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.36

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 Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09361565).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RENBP	NM_002910.6	c.464C>T	p.Thr155Met	missense_variant, splice_region_variant	6/11	ENST00000393700.8
RENBP	XM_017029698.2	c.434C>T	p.Thr145Met	missense_variant, splice_region_variant	6/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RENBP	ENST00000393700.8	c.464C>T	p.Thr155Met	missense_variant, splice_region_variant	6/11	1	NM_002910.6	P1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.0000116 AC: 12 AN: 1031925 Hom.: 0 Cov.: 30 AF XY: 0.0000126 AC XY: 4 AN XY: 318269

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000349

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000124

Gnomad4 OTH exome AF: 0.0000231

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 27, 2022

The c.464C>T (p.T155M) alteration is located in exon 6 (coding exon 6) of the RENBP gene. This alteration results from a C to T substitution at nucleotide position 464, causing the threonine (T) at amino acid position 155 to be replaced by a methionine (M). 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	0.084
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.0
Dann	Benign	0.97
DEOGEN2	Benign	0.20	T;.
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.56	T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.094	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.81	N;N
REVEL	Benign	0.071
Sift	Benign	0.094	T;T
Sift4G	Benign	0.10	T;T
Polyphen		0.95	P;.
Vest4		0.15
MutPred		0.36		Gain of helix (P = 6e-04);.;
MVP		0.082
MPC		0.74
ClinPred		0.28	T
GERP RS		-2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.022
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000073
dbscSNV1_RF	Benign	0.060
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: rs2065234833; hg19: chrX-153208530; COSMIC: COSV60075098; COSMIC: COSV60075098;