19-12826851-T-C

Position:

chr19-12826851-T-C

Variant summary

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

The NM_001270441.2(RTBDN):c.386A>G(p.Asp129Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000038 in 1,552,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

RTBDN
NM_001270441.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.603

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:

(HGNC:):

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1036315).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTBDN	NM_001270441.2 linkuse as main transcript	c.386A>G	p.Asp129Gly	missense_variant	5/6	ENST00000674343.2	NP_001257370.2
LOC105372281	XR_936336.2 linkuse as main transcript	n.66T>C		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTBDN	ENST00000674343.2 linkuse as main transcript	c.386A>G	p.Asp129Gly	missense_variant	5/6		NM_001270441.2	ENSP00000501410	A2	Q9BSG5-1
	ENST00000588469.1 linkuse as main transcript	n.269T>C		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000918

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000250

AC:

AN:

159810

Hom.:

AF XY:

0.0000237

AC XY:

AN XY:

84276

show subpopulations

Gnomad AFR exome

AF:

0.000331

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:

0.0000159

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000143

AC:

AN:

1400244

Hom.:

Cov.:

AF XY:

0.0000203

AC XY:

AN XY:

690952

show subpopulations

Gnomad4 AFR exome

AF:

0.000443

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000278

Gnomad4 OTH exome

AF:

0.0000345

GnomAD4 genome

AF:

0.000256

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.000915

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000777

Hom.:

Bravo

AF:

0.000246

ESP6500AA

AF:

0.000690

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000473

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

Sep 06, 2022

The c.482A>G (p.D161G) alteration is located in exon 6 (coding exon 6) of the RTBDN gene. This alteration results from a A to G substitution at nucleotide position 482, causing the aspartic acid (D) at amino acid position 161 to be replaced by a glycine (G). 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

Pathogenic

0.68

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.090

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.27

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

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.79

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

M_CAP

Benign

0.052

MetaRNN

Benign

0.10

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

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

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

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.44

PROVEAN

Pathogenic

-6.4

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

REVEL

Uncertain

0.46

Sift

Uncertain

0.0080

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

Sift4G

Benign

0.084

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

Polyphen

1.0

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

Vest4

0.63

MVP

0.69

MPC

1.2

ClinPred

0.26

GERP RS

2.1

Varity_R

0.39

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