12-55723916-C-T

Variant names:

• chr12-55723916-C-T
• NM_002905.5:c.600C>T
• RDH5 p.Val200Val

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_002905.5(RDH5):​c.600C>T​(p.Val200Val) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V200V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RDH5 NM_002905.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.945
• Publications: 0 publications found

Genes affected

RDH5 (HGNC:9940): (retinol dehydrogenase 5) This gene encodes an enzyme belonging to the short-chain dehydrogenases/reductases (SDR) family. This retinol dehydrogenase functions to catalyze the final step in the biosynthesis of 11-cis retinaldehyde, which is the universal chromophore of visual pigments. Mutations in this gene cause autosomal recessive fundus albipunctatus, a rare form of night blindness that is characterized by a delay in the regeneration of cone and rod photopigments. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the neighboring upstream BLOC1S1 (biogenesis of lysosomal organelles complex-1, subunit 1) gene. [provided by RefSeq, Dec 2010]

ENSG00000258311 (HGNC:):

CD63 (HGNC:1692): (CD63 molecule) The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. The encoded protein is a cell surface glycoprotein that is known to complex with integrins. It may function as a blood platelet activation marker. Deficiency of this protein is associated with Hermansky-Pudlak syndrome. Also this gene has been associated with tumor progression. Alternative splicing results in multiple transcript variants encoding different protein isoforms. [provided by RefSeq, Apr 2012]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP7: Synonymous conserved (PhyloP=-0.945 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002905.5. 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
	RDH5	NM_002905.5	MANE Select	c.600C>T	p.Val200Val	synonymous	Exon 4 of 5	NP_002896.2	Q92781
	RDH5	NM_001199771.3		c.600C>T	p.Val200Val	synonymous	Exon 4 of 5	NP_001186700.1	Q92781
	CD63	NM_001413284.1		c.*1148G>A		3_prime_UTR	Exon 9 of 9	NP_001400213.1	P08962-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RDH5	ENST00000257895.10	TSL:1 MANE Select	c.600C>T	p.Val200Val	synonymous	Exon 4 of 5	ENSP00000257895.6	Q92781
	RDH5	ENST00000548082.1	TSL:1	c.600C>T	p.Val200Val	synonymous	Exon 4 of 5	ENSP00000447128.1	Q92781
	ENSG00000258311	ENST00000550412.5	TSL:2	c.*2210C>T		3_prime_UTR	Exon 4 of 4	ENSP00000447650.1	F8W036

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	10
DANN	Benign	0.88
PhyloP100		-0.94

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-56117700;