chr19-12828669-A-G

Position:

• chr19-12828669-A-G

Variant summary

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

The NM_001270441.2(RTBDN):​c.353T>C​(p.Leu118Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 3.83

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTBDN	NM_001270441.2	c.353T>C	p.Leu118Pro	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.353T>C	p.Leu118Pro	missense_variant	4/6		NM_001270441.2	ENSP00000501410.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Jan 16, 2024

The c.449T>C (p.L150P) alteration is located in exon 5 (coding exon 5) of the RTBDN gene. This alteration results from a T to C substitution at nucleotide position 449, causing the leucine (L) at amino acid position 150 to be replaced by a proline (P). 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	0.75
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.067	T;.;.;.;T;.;.;T;.;T;T
Eigen	Benign	0.17
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.72	T;T;T;T;.;T;T;T;T;T;T
M_CAP	Uncertain	0.092	D
MetaRNN	Uncertain	0.72	D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.3	M;.;.;.;M;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;N
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-4.3	.;.;.;D;D;.;.;.;.;.;.
REVEL	Uncertain	0.64
Sift	Uncertain	0.0050	.;.;.;D;D;.;.;.;.;.;.
Sift4G	Uncertain	0.0070	D;D;D;D;D;D;.;.;.;D;.
Polyphen		1.0	D;.;.;D;D;.;.;.;.;.;.
Vest4		0.81
MutPred		0.65		Gain of catalytic residue at L118 (P = 0.0101);.;.;.;Gain of catalytic residue at L118 (P = 0.0101);Gain of catalytic residue at L118 (P = 0.0101);.;Gain of catalytic residue at L118 (P = 0.0101);.;.;Gain of catalytic residue at L118 (P = 0.0101);
MVP		0.76
MPC		1.4
ClinPred		0.98	D
GERP RS		3.3
Varity_R		0.79
gMVP		0.92

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: chr19-12939483; COSMIC: COSV104646146; COSMIC: COSV104646146;