chr19-12828751-C-G

Variant names:

• chr19-12828751-C-G
• NM_001270441.2:c.271G>C

Variant summary

Our verdict is Uncertain significance. The variant received 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. 17/22 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
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13566726).

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.271G>C	p.Glu91Gln	missense	Exon 4 of 6	NP_001257370.2	Q9BSG5-1
	RTBDN	NM_031429.3		c.367G>C	p.Glu123Gln	missense	Exon 5 of 7	NP_113617.1	Q9BSG5-2
	RTBDN	NM_001270442.2		c.289G>C	p.Glu97Gln	missense	Exon 4 of 6	NP_001257371.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTBDN	ENST00000674343.2	MANE Select	c.271G>C	p.Glu91Gln	missense	Exon 4 of 6	ENSP00000501410.1	Q9BSG5-1
	RTBDN	ENST00000322912.9	TSL:1	c.367G>C	p.Glu123Gln	missense	Exon 5 of 7	ENSP00000326253.4	Q9BSG5-2
	RTBDN	ENST00000592204.5	TSL:1	c.301G>C	p.Glu101Gln	missense	Exon 4 of 6	ENSP00000466765.1	Q9BSG5-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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	0.093
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.0016	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	N
PhyloP100		0.66
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.17
Sift	Benign	0.38	T
Sift4G	Benign	0.28	T
Polyphen		0.0060	B
Vest4		0.11
MutPred		0.40		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
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

hg19: chr19-12939565;