19-12828751-C-G

Position:

• chr19-12828751-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001270441.2(RTBDN):​c.271G>C​(p.Glu91Gln) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RTBDN NM_001270441.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.658

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]

ENSG00000267424 (HGNC:):

ACMG classification

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=0.13566726).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTBDN	NM_001270441.2	c.271G>C	p.Glu91Gln	missense_variant	4/6	ENST00000674343.2	NP_001257370.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTBDN	ENST00000674343.2	c.271G>C	p.Glu91Gln	missense_variant	4/6		NM_001270441.2	ENSP00000501410.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 16, 2023

The c.367G>C (p.E123Q) alteration is located in exon 5 (coding exon 5) of the RTBDN gene. This alteration results from a G to C substitution at nucleotide position 367, causing the glutamic acid (E) at amino acid position 123 to be replaced by a glutamine (Q). 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	0.093
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.0016	T;.;.;.;T;.;.;T;.;T;T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.68	T;T;T;T;.;T;T;T;T;T;T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.14	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	N;.;.;.;N;.;.;.;.;.;.
MutationTaster	Benign	0.88	D;N;N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.13	.;.;.;N;N;.;.;.;.;.;.
REVEL	Benign	0.17
Sift	Benign	0.38	.;.;.;T;T;.;.;.;.;.;.
Sift4G	Benign	0.28	T;T;T;T;T;T;.;.;.;T;.
Polyphen		0.0060	B;.;.;B;B;.;.;.;.;.;.
Vest4		0.11
MutPred		0.40		Gain of MoRF binding (P = 0.0472);.;.;.;Gain of MoRF binding (P = 0.0472);Gain of MoRF binding (P = 0.0472);.;Gain of MoRF binding (P = 0.0472);.;.;Gain of MoRF binding (P = 0.0472);
MVP		0.62
MPC		0.38
ClinPred		0.087	T
GERP RS		-0.91
Varity_R		0.10
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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.

Other links and lift over

hg19: chr19-12939565;