NM_020905.4:c.114dupC

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP5

The NM_020905.4(RDH14):c.114dupC(p.Gly39ArgfsTer97) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000634 in 1,513,300 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000061 ( 0 hom. )

Consequence

RDH14
NM_020905.4 frameshift

Scores

Not classified

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: -0.0850

Publications

1 publications found

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]

RDH14 links:

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]

NT5C1B-RDH14 links:

LOC105373456 (HGNC:):

LOC105373456 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 2-18560458-C-CG is Pathogenic according to our data. Variant chr2-18560458-C-CG is described in CliVar as Likely_pathogenic. Clinvar id is 827760.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-18560458-C-CG is described in CliVar as Likely_pathogenic. Clinvar id is 827760.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-18560458-C-CG is described in CliVar as Likely_pathogenic. Clinvar id is 827760.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-18560458-C-CG is described in CliVar as Likely_pathogenic. Clinvar id is 827760.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-18560458-C-CG is described in CliVar as Likely_pathogenic. Clinvar id is 827760.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-18560458-C-CG is described in CliVar as Likely_pathogenic. Clinvar id is 827760.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-18560458-C-CG is described in CliVar as Likely_pathogenic. Clinvar id is 827760.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-18560458-C-CG is described in CliVar as Likely_pathogenic. Clinvar id is 827760.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RDH14	NM_020905.4 link	c.114dupC	p.Gly39ArgfsTer97	frameshift_variant	Exon 1 of 2	ENST00000381249.4	NP_065956.1	Q9HBH5Q53RX3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RDH14	ENST00000381249.4 link	c.114dupC	p.Gly39ArgfsTer97	frameshift_variant	Exon 1 of 2	1	NM_020905.4	ENSP00000370648.3	Q9HBH5
NT5C1B-RDH14	ENST00000532967.5 link	c.1784+3386dupC		intron_variant	Intron 10 of 10	2		ENSP00000433415.1
NT5C1B-RDH14	ENST00000444297.2 link	c.1336-4651dupC		intron_variant	Intron 8 of 8	2		ENSP00000412639.2	C9J2C7
RDH14	ENST00000468071.1 link	n.50+171dupC		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000103

AC:

AN:

106904

AF XY:

0.000101

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000386

Gnomad NFE exome

AF:

0.0000757

Gnomad OTH exome

AF:

0.000300

GnomAD4 exome

AF:

0.0000610

AC:

AN:

1361032

Hom.:

Cov.:

AF XY:

0.0000611

AC XY:

AN XY:

671580

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28116

American (AMR)

AF:

0.0000298

AC:

AN:

33506

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24232

East Asian (EAS)

AF:

0.00

AC:

AN:

32666

South Asian (SAS)

AF:

0.000129

AC:

AN:

77246

European-Finnish (FIN)

AF:

0.000660

AC:

AN:

33330

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4170

European-Non Finnish (NFE)

AF:

0.0000420

AC:

AN:

1070952

Other (OTH)

AF:

0.0000880

AC:

AN:

56814

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41574

American (AMR)

AF:

0.0000653

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000194

AC:

AN:

5152

South Asian (SAS)

AF:

0.000414

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68002

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Cerebellar atrophy;C3714756:Intellectual disability

Pathogenic:1

Mar 03, 2020

Molecular Neuropsychiatry & Development Lab, Centre for Addiction and Mental Health

Significance:Likely pathogenic

Review Status:no assertion criteria provided

Collection Method:research

The NM_020905.3:c.114dup/ Gly39Argfs*97 biallelic variant in RDH14 is reported segregating in two affected members of a single large family from Pakistan (Pastore et al, submitted). The variant is predicted to lead to premature truncation of the protein with loss of function, along with nonsense-mediated mRNA decay. No corroborative evidence from other families, or from animal models is available as yet, and thus there remain reservations as to the pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.085

Mutation Taster

=59/141

disease causing (ClinVar)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over