3-139518470-T-G

Position:

• chr3-139518470-T-G

Variant summary

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

The NM_002899.5(RBP1):​c.491A>C​(p.Lys164Thr) 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: RBP1 NM_002899.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.72

Genes affected

RBP1 (HGNC:9919): (retinol binding protein 1) This gene encodes the carrier protein involved in the transport of retinol (vitamin A alcohol) from the liver storage site to peripheral tissue. Vitamin A is a fat-soluble vitamin necessary for growth, reproduction, differentiation of epithelial tissues, and vision. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

COPB2-DT (HGNC:55579): (COPB2 divergent transcript)

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	UniProt
RBP1	NM_002899.5	c.491A>C	p.Lys164Thr	missense_variant	3/4	ENST00000672186.1
COPB2-DT	NR_121609.1	n.355-59322T>G		intron_variant, non_coding_transcript_variant
RBP1	NM_001365940.2	c.305A>C	p.Lys102Thr	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBP1	ENST00000672186.1	c.491A>C	p.Lys164Thr	missense_variant	3/4		NM_002899.5
COPB2-DT	ENST00000658348.1	n.672-59322T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 30, 2022

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with RBP1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 164 of the RBP1 protein (p.Lys164Thr). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.081	T;T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Pathogenic	0.97	D;D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.49	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.5	.;H
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-4.8	D;.
REVEL	Benign	0.22
Sift	Benign	0.079	T;.
Sift4G	Uncertain	0.026	D;T
Polyphen		0.89	.;P
Vest4		0.48
MutPred		0.50		.;Loss of methylation at K102 (P = 0.0185);
MVP		0.58
MPC		1.4
ClinPred		0.99	D
GERP RS		5.9
Varity_R		0.86
gMVP		0.74

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.

Other links and lift over

hg19: chr3-139237312;