Genetic Variant RDH14:p.Gly39AlafsTer9 (chr2-18560458-CG-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020905.4(RDH14):c.114delC(p.Gly39AlafsTer9) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000735 in 1,361,022 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

RDH14
NM_020905.4 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RDH14	NM_020905.4 link	c.114delC	p.Gly39AlafsTer9	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.114delC	p.Gly39AlafsTer9	frameshift_variant	Exon 1 of 2	1	NM_020905.4	ENSP00000370648.3	Q9HBH5
NT5C1B-RDH14	ENST00000532967.5 link	c.1784+3386delC		intron_variant	Intron 10 of 10	2		ENSP00000433415.1
NT5C1B-RDH14	ENST00000444297.2 link	c.1336-4651delC		intron_variant	Intron 8 of 8	2		ENSP00000412639.2	C9J2C7
RDH14	ENST00000468071.1 link	n.50+171delC		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.35e-7

AC:

AN:

1361022

Hom.:

Cov.:

AF XY:

0.00000149

AC XY:

AN XY:

671578

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28116

American (AMR)

AF:

0.00

AC:

AN:

33504

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24230

East Asian (EAS)

AF:

0.00

AC:

AN:

32666

South Asian (SAS)

AF:

0.00

AC:

AN:

77246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33330

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4170

European-Non Finnish (NFE)

AF:

9.34e-7

AC:

AN:

1070946

Other (OTH)

AF:

0.00

AC:

AN:

56814

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.085

Mutation Taster

=55/145

disease causing (fs/PTC)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over