2-18560290-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.283G>A​(p.Ala95Thr) 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. 14/20 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)
Exomes 𝑓: 0.0000023 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

RDH14
NM_020905.4 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.707
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=0.1023047).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RDH14NM_020905.4 linkc.283G>A p.Ala95Thr 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.283G>A p.Ala95Thr missense_variant Exon 1 of 2 1 NM_020905.4 ENSP00000370648.3 Q9HBH5
NT5C1B-RDH14ENST00000532967.5 linkc.1784+3555G>A intron_variant Intron 10 of 10 2 ENSP00000433415.1
NT5C1B-RDH14ENST00000444297.2 linkc.1336-4482G>A intron_variant Intron 8 of 8 2 ENSP00000412639.2 C9J2C7
RDH14ENST00000468071.1 linkn.50+340G>A intron_variant Intron 1 of 1 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000225
AC:
3
AN:
1332944
Hom.:
0
Cov.:
31
AF XY:
0.00000305
AC XY:
2
AN XY:
656710
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000339
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.45e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 25, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.283G>A (p.A95T) 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 283, causing the alanine (A) at amino acid position 95 to be replaced by a threonine (T). 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
0.080
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
12
DANN
Benign
0.89
DEOGEN2
Benign
0.20
T
Eigen
Benign
-0.91
Eigen_PC
Benign
-0.90
FATHMM_MKL
Benign
0.14
N
LIST_S2
Benign
0.41
T
M_CAP
Pathogenic
0.51
D
MetaRNN
Benign
0.10
T
MetaSVM
Benign
-0.87
T
MutationAssessor
Benign
0.51
N
PROVEAN
Benign
0.17
N
REVEL
Benign
0.10
Sift
Benign
0.48
T
Sift4G
Benign
0.51
T
Polyphen
0.030
B
Vest4
0.047
MutPred
0.34
Gain of phosphorylation at A95 (P = 0.0475);
MVP
0.83
MPC
0.044
ClinPred
0.082
T
GERP RS
2.3
Varity_R
0.037
gMVP
0.21

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

LitVar

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

Other links and lift over

dbSNP: rs1411455434; hg19: chr2-18741556; API