Variant chr19-12826809-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001270441.2(RTBDN):c.428G>T(p.Arg143Met) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RTBDN
NM_001270441.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.05

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:

ENSG00000267424 (HGNC:58174):

ENSG00000267424 links:

LOC105372281 (HGNC:):

LOC105372281 links:

HOOK2 (HGNC:19885): (hook microtubule tethering protein 2) Hook proteins are cytosolic coiled-coil proteins that contain conserved N-terminal domains, which attach to microtubules, and more divergent C-terminal domains, which mediate binding to organelles. The Drosophila Hook protein is a component of the endocytic compartment.[supplied by OMIM, Apr 2004]

HOOK2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33872372).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTBDN	NM_001270441.2 link	c.428G>T	p.Arg143Met	missense_variant	5/6	ENST00000674343.2	NP_001257370.2	Q9BSG5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTBDN	ENST00000674343.2 link	c.428G>T	p.Arg143Met	missense_variant	5/6		NM_001270441.2	ENSP00000501410.1		Q9BSG5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1402976

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

692538

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Nov 13, 2024

The c.524G>T (p.R175M) alteration is located in exon 6 (coding exon 6) of the RTBDN gene. This alteration results from a G to T substitution at nucleotide position 524, causing the arginine (R) at amino acid position 175 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

0.26

BayesDel_addAF

Uncertain

0.037

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.058

T;.;.;.;T;.;.;T;.;T

Eigen

Benign

-0.0041

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.70

T;T;T;T;.;T;T;T;T;T

M_CAP

Benign

0.066

MetaRNN

Benign

0.34

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.42

MutationAssessor

Uncertain

2.3

M;.;.;.;M;.;.;.;.;.

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-3.3

.;.;.;D;D;.;.;.;.;.

REVEL

Uncertain

0.36

Sift

Uncertain

0.0030

.;.;.;D;D;.;.;.;.;.

Sift4G

Uncertain

0.0030

D;D;D;D;D;D;.;.;.;D

Polyphen

1.0

D;.;.;D;D;.;.;.;.;.

Vest4

0.55

MutPred

0.51

Loss of methylation at K142 (P = 0.0244);.;.;.;Loss of methylation at K142 (P = 0.0244);Loss of methylation at K142 (P = 0.0244);.;Loss of methylation at K142 (P = 0.0244);.;.;

MVP

0.63

MPC

1.1

ClinPred

0.90

GERP RS

3.2

Varity_R

0.23

gMVP

0.73

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over