Variant 12-7128738-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_031491.4(RBP5):c.38C>T(p.Ser13Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000227 in 1,452,814 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

RBP5
NM_031491.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.97

Variant links:

Genes affected

RBP5 (HGNC:15847): (retinol binding protein 5) The protein encoded by this gene is a cellular retinol-binding protein expressed highly in kidney and liver. Down-regulation of the encoded protein in hepatocellular carcinoma was associated with large tumor size and poor patient survival rates. [provided by RefSeq, Jul 2016]

RBP5 links:

RBP5 (HGNC:):

RBP5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBP5	NM_031491.4 linkuse as main transcript	c.38C>T	p.Ser13Leu	missense_variant	1/4	ENST00000266560.8	NP_113679.1	P82980

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RBP5	ENST00000266560.8 linkuse as main transcript	c.38C>T	p.Ser13Leu	missense_variant	1/4	1	NM_031491.4	ENSP00000266560.3	P82980
RBP5	ENST00000542370.1 linkuse as main transcript	c.38C>T	p.Ser13Leu	missense_variant	1/3	2		ENSP00000438083.1	A0A0B4J233
RBP5	ENST00000543045.1 linkuse as main transcript	n.38C>T		non_coding_transcript_exon_variant	1/3	2		ENSP00000445483.1	F5H2Q2
RBP5	ENST00000619522.2 linkuse as main transcript	n.152C>T		non_coding_transcript_exon_variant	1/4	6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000128

AC:

AN:

234858

Hom.:

AF XY:

0.00000791

AC XY:

AN XY:

126402

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000576

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000188

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000227

AC:

AN:

1452814

Hom.:

Cov.:

AF XY:

0.0000194

AC XY:

AN XY:

721610

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000298

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.0000227

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 25, 2024

The c.38C>T (p.S13L) alteration is located in exon 1 (coding exon 1) of the RBP5 gene. This alteration results from a C to T substitution at nucleotide position 38, causing the serine (S) at amino acid position 13 to be replaced by a leucine (L). 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

0.23

BayesDel_addAF

Benign

-0.0015

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.15

T;T

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.032

MetaRNN

Uncertain

0.57

D;D

MetaSVM

Benign

-0.92

MutationAssessor

Pathogenic

3.6

H;.

PrimateAI

Uncertain

0.61

PROVEAN

Pathogenic

-4.6

D;D

REVEL

Benign

0.20

Sift

Uncertain

0.0050

D;D

Sift4G

Uncertain

0.0030

D;D

Polyphen

1.0

D;.

Vest4

0.53

MutPred

0.50

Gain of catalytic residue at Y8 (P = 0.0236);Gain of catalytic residue at Y8 (P = 0.0236);

MVP

0.19

MPC

0.76

ClinPred

0.99

GERP RS

3.3

Varity_R

0.81

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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