2-18560238-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020905.4(RDH14):​c.335G>A​(p.Arg112Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000328 in 1,525,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

RDH14
NM_020905.4 missense

Scores

3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.719
Variant links:
Genes affected
RDH14 (HGNC:19979): (retinol dehydrogenase 14) Enables NADP-retinol dehydrogenase activity. Involved in osteoblast differentiation. Located in cytosol; endoplasmic reticulum; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
NT5C1B-RDH14 (HGNC:38831): (NT5C1B-RDH14 readthrough) This locus represents naturally occurring read-through transcription between the neighboring NT5C1B (5'-nucleotidase, cytosolic IB) and RDH14 (retinol dehydrogenase 14) genes on chromosome 2. Alternative splicing results in multiple transcript variants, one of which encodes a fusion protein that shares sequence identity with the products of each individual gene. [provided by RefSeq, Nov 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.15315592).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RDH14NM_020905.4 linkc.335G>A p.Arg112Gln missense_variant Exon 1 of 2 ENST00000381249.4 NP_065956.1 Q9HBH5Q53RX3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RDH14ENST00000381249.4 linkc.335G>A p.Arg112Gln missense_variant Exon 1 of 2 1 NM_020905.4 ENSP00000370648.3 Q9HBH5
NT5C1B-RDH14ENST00000532967.5 linkc.1784+3607G>A intron_variant Intron 10 of 10 2 ENSP00000433415.1
NT5C1B-RDH14ENST00000444297.2 linkc.1336-4430G>A intron_variant Intron 8 of 8 2 ENSP00000412639.2 C9J2C7
RDH14ENST00000468071.1 linkn.50+392G>A intron_variant Intron 1 of 1 2

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152168
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000146
AC:
2
AN:
1373352
Hom.:
0
Cov.:
31
AF XY:
0.00000148
AC XY:
1
AN XY:
677738
show subpopulations
Gnomad4 AFR exome
AF:
0.0000666
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152168
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 07, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.335G>A (p.R112Q) alteration is located in exon 1 (coding exon 1) of the RDH14 gene. This alteration results from a G to A substitution at nucleotide position 335, causing the arginine (R) at amino acid position 112 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
0.21
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
15
DANN
Uncertain
0.99
DEOGEN2
Benign
0.22
T
Eigen
Benign
-0.69
Eigen_PC
Benign
-0.78
FATHMM_MKL
Benign
0.11
N
LIST_S2
Uncertain
0.97
D
M_CAP
Uncertain
0.20
D
MetaRNN
Benign
0.15
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.0
L
PROVEAN
Benign
-1.0
N
REVEL
Benign
0.077
Sift
Benign
0.036
D
Sift4G
Benign
0.061
T
Polyphen
0.81
P
Vest4
0.21
MutPred
0.58
Loss of sheet (P = 0.1158);
MVP
0.16
MPC
0.064
ClinPred
0.42
T
GERP RS
-2.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.084
gMVP
0.29

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1450009325; hg19: chr2-18741504; API