chr19-12826809-C-A

Variant names:

• chr19-12826809-C-A
• NM_001270441.2:c.428G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

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. 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.05
• Publications: 0 publications found

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-AS1 (HGNC:58174):

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33872372).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270441.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTBDN	NM_001270441.2	MANE Select	c.428G>T	p.Arg143Met	missense	Exon 5 of 6	NP_001257370.2	Q9BSG5-1
	RTBDN	NM_031429.3		c.524G>T	p.Arg175Met	missense	Exon 6 of 7	NP_113617.1	Q9BSG5-2
	RTBDN	NM_001270442.2		c.446G>T	p.Arg149Met	missense	Exon 5 of 6	NP_001257371.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTBDN	ENST00000674343.2	MANE Select	c.428G>T	p.Arg143Met	missense	Exon 5 of 6	ENSP00000501410.1	Q9BSG5-1
	RTBDN	ENST00000322912.9	TSL:1	c.524G>T	p.Arg175Met	missense	Exon 6 of 7	ENSP00000326253.4	Q9BSG5-2
	RTBDN	ENST00000592204.5	TSL:1	c.458G>T	p.Arg153Met	missense	Exon 5 of 6	ENSP00000466765.1	Q9BSG5-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1402976 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 692538

African (AFR) AF: 0.00 AC: 0 AN: 31716

American (AMR) AF: 0.00 AC: 0 AN: 36408

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25222

East Asian (EAS) AF: 0.00 AC: 0 AN: 36006

South Asian (SAS) AF: 0.00 AC: 0 AN: 79422

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4986

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1081580

Other (OTH) AF: 0.00 AC: 0 AN: 58104

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.058	T
Eigen	Benign	-0.0041
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.0
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.55
MutPred		0.51		Loss of methylation at K142 (P = 0.0244)
MVP		0.63
MPC		1.1
ClinPred		0.90	D
GERP RS		3.2
Varity_R		0.23
gMVP		0.73
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

hg19: chr19-12937623;