Variant 10-93593997-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate

The NM_006744.4(RBP4):c.394T>A(p.Tyr132Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RBP4
NM_006744.4 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 9.29

Variant links:

Genes affected

RBP4 (HGNC:9922): (retinol binding protein 4) This protein belongs to the lipocalin family and is the specific carrier for retinol (vitamin A alcohol) in the blood. It delivers retinol from the liver stores to the peripheral tissues. In plasma, the RBP-retinol complex interacts with transthyretin which prevents its loss by filtration through the kidney glomeruli. A deficiency of vitamin A blocks secretion of the binding protein posttranslationally and results in defective delivery and supply to the epidermal cells. [provided by RefSeq, Jul 2008]

RBP4 links:

FFAR4 (HGNC:19061): (free fatty acid receptor 4) This gene encodes a G protein-coupled receptor (GPR) which belongs to the rhodopsin family of GPRs. The encoded protein functions as a receptor for free fatty acids, including omega-3, and participates in suppressing anti-inflammatory responses and insulin sensitizing. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

FFAR4 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.967

PP5

Variant 10-93593997-A-T is Pathogenic according to our data. Variant chr10-93593997-A-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 430902.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBP4	NM_006744.4 linkuse as main transcript	c.394T>A	p.Tyr132Asn	missense_variant	5/6	ENST00000371464.8	NP_006735.2	P02753
RBP4	NM_001323517.1 linkuse as main transcript	c.394T>A	p.Tyr132Asn	missense_variant	5/6		NP_001310446.1	P02753
RBP4	NM_001323518.2 linkuse as main transcript	c.388T>A	p.Tyr130Asn	missense_variant	5/6		NP_001310447.1	P02753Q5VY30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RBP4	ENST00000371464.8 linkuse as main transcript	c.394T>A	p.Tyr132Asn	missense_variant	5/6	1	NM_006744.4	ENSP00000360519.3	P02753
RBP4	ENST00000371467.5 linkuse as main transcript	c.394T>A	p.Tyr132Asn	missense_variant	5/6	5		ENSP00000360522.1	P02753
RBP4	ENST00000371469.2 linkuse as main transcript	c.388T>A	p.Tyr130Asn	missense_variant	5/6	5		ENSP00000360524.2	Q5VY30
FFAR4	ENST00000604414.1 linkuse as main transcript	c.697-10077A>T		intron_variant		3		ENSP00000474477.1	S4R3L2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461582

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727092

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Unilateral microphthalmos

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Genetics Department, University Hospital of Toulouse

Dec 06, 2022

PM2, PP2, PP3, PP5 -

Congenital ocular coloboma;C0026010:Microphthalmia

Pathogenic:1

Pathogenic, no assertion criteria provided

clinical testing

Fundació de Recerca de l'Institut de Microcirurgia Ocular

Apr 01, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Pathogenic

0.35

BayesDel_noAF

Pathogenic

0.27

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.47

T;T;T;T

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.86

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

.;D;D;.

M_CAP

Uncertain

0.20

MetaRNN

Pathogenic

0.97

D;D;D;D

MetaSVM

Pathogenic

0.92

MutationAssessor

Uncertain

2.4

M;M;.;.

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-8.2

D;D;.;D

REVEL

Pathogenic

0.89

Sift

Uncertain

0.0030

D;D;.;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;D;.;.

Vest4

0.95

MutPred

0.79

Loss of phosphorylation at Y132 (P = 0.0832);Loss of phosphorylation at Y132 (P = 0.0832);.;.;

MVP

0.85

MPC

2.0

ClinPred

0.99

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.95

gMVP

0.94

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

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