Variant 19-12834832-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031429.3(RTBDN):c.31A>G(p.Thr11Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RTBDN
NM_031429.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.130

Variant links:

Genes affected

RTBDN (HGNC:30310): (retbindin) This gene was first identified in a study of human eye tissues. The protein encoded by this gene is preferentially expressed in the retina and may play a role in binding retinoids and other carotenoids as it shares homology with riboflavin binding proteins. Alternative splicing results in multiple transcript variants and protein isoforms. [provided by RefSeq, Jul 2012]

RTBDN links:

MAST1 (HGNC:19034): (microtubule associated serine/threonine kinase 1) This gene is a member of the microtubule-associated serine/threonine kinase (MAST) family. The protein encoded by this gene has an N-terminal serine/threonine kinase domain followed by a postsynaptic density protein-95/discs large/zona occludens-1 (PDZ) domain. In mouse and rat, the orthologous protein associates with the cytoskeleton and can bind both beta-2-syntrophin and neuronal nitric oxide synthase (nNOS) through its PDZ domain. In mouse and rat, this protein also co-localizes with dystrophin- and utrophin-associated protein complexes (DAPC/UAPC) in the vascular endothelium of the central nervous system. [provided by RefSeq, May 2017]

MAST1 links:

HOOK2 (HGNC:):

HOOK2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07019541).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTBDN	NM_031429.3 linkuse as main transcript	c.31A>G	p.Thr11Ala	missense_variant	2/7		NP_113617.1	Q9BSG5-2
RTBDN	NM_001270440.2 linkuse as main transcript	c.31A>G	p.Thr11Ala	missense_variant	2/7		NP_001257369.1	Q8N210K7ESG0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	UniProt
RTBDN	ENST00000322912.9 linkuse as main transcript	c.31A>G	p.Thr11Ala	missense_variant	2/7	1	ENSP00000326253.4	Q9BSG5-2
RTBDN	ENST00000589272.5 linkuse as main transcript	c.31A>G	p.Thr11Ala	missense_variant	2/7	2	ENSP00000468697.1	K7ESG0
RTBDN	ENST00000587549.1 linkuse as main transcript	c.31A>G	p.Thr11Ala	missense_variant	2/4	3	ENSP00000468769.1	K7ESL8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251484

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727246

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.:

Alfa

AF:

0.0000370

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

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

Jun 13, 2023

The c.31A>G (p.T11A) alteration is located in exon 2 (coding exon 2) of the RTBDN gene. This alteration results from a A to G substitution at nucleotide position 31, causing the threonine (T) at amino acid position 11 to be replaced by an alanine (A). 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

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.66

CADD

Benign

5.5

DANN

Benign

0.97

DEOGEN2

Benign

0.011

.;.;T

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.076

LIST_S2

Benign

0.40

T;T;T

M_CAP

Benign

0.0027

MetaRNN

Benign

0.070

T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.33

PROVEAN

Benign

0.020

.;N;.

REVEL

Benign

0.024

Sift

Pathogenic

0.0

.;D;.

Sift4G

Pathogenic

0.0

D;D;.

Polyphen

0.21

.;B;.

Vest4

0.15

MVP

0.099

MPC

0.57

ClinPred

0.24

GERP RS

-0.34

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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