12-55723916-C-G

Variant names:

• chr12-55723916-C-G
• rs13193
• NM_002905.5:c.600C>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002905.5(RDH5):​c.600C>G​(p.Val200Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0523 in 1,613,962 control chromosomes in the GnomAD database, including 6,787 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. V200V) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.13 (2700 hom., cov: 32)
  • Exomes 𝑓: 0.044 (4087 hom.)
• Consequence: RDH5 NM_002905.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.945
• Publications: 12 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 12-55723916-C-G is Benign according to our data. Variant chr12-55723916-C-G is described in ClinVar as Benign. ClinVar VariationId is 258858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.945 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RDH5	NM_002905.5	MANE Select	c.600C>G	p.Val200Val	synonymous	Exon 4 of 5	NP_002896.2
	RDH5	NM_001199771.3		c.600C>G	p.Val200Val	synonymous	Exon 4 of 5	NP_001186700.1
	CD63	NM_001413284.1		c.*1148G>C		3_prime_UTR	Exon 9 of 9	NP_001400213.1

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19905 AN: 152126 Hom.: 2693 Cov.: 32

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.0662

Gnomad EAS AF: 0.0275

Gnomad SAS AF: 0.0616

Gnomad FIN AF: 0.0322

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0287

Gnomad OTH AF: 0.113

GnomAD2 exomes AF: 0.0821 AC: 20639 AN: 251260 AF XY: 0.0713

Gnomad AFR exome AF: 0.345

Gnomad AMR exome AF: 0.218

Gnomad ASJ exome AF: 0.0647

Gnomad EAS exome AF: 0.0265

Gnomad FIN exome AF: 0.0291

Gnomad NFE exome AF: 0.0291

Gnomad OTH exome AF: 0.0684

GnomAD4 exome AF: 0.0441 AC: 64532 AN: 1461718 Hom.: 4087 Cov.: 31 AF XY: 0.0431 AC XY: 31349 AN XY: 727174

African (AFR) AF: 0.344 AC: 11524 AN: 33476

American (AMR) AF: 0.209 AC: 9350 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0618 AC: 1614 AN: 26134

East Asian (EAS) AF: 0.0189 AC: 750 AN: 39698

South Asian (SAS) AF: 0.0631 AC: 5440 AN: 86250

European-Finnish (FIN) AF: 0.0283 AC: 1506 AN: 53284

Middle Eastern (MID) AF: 0.104 AC: 600 AN: 5768

European-Non Finnish (NFE) AF: 0.0271 AC: 30166 AN: 1111996

Other (OTH) AF: 0.0593 AC: 3582 AN: 60392

GnomAD4 genome AF: 0.131 AC: 19936 AN: 152244 Hom.: 2700 Cov.: 32 AF XY: 0.130 AC XY: 9708 AN XY: 74458

African (AFR) AF: 0.338 AC: 14034 AN: 41492

American (AMR) AF: 0.171 AC: 2612 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0662 AC: 230 AN: 3472

East Asian (EAS) AF: 0.0276 AC: 143 AN: 5180

South Asian (SAS) AF: 0.0617 AC: 298 AN: 4830

European-Finnish (FIN) AF: 0.0322 AC: 342 AN: 10630

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0287 AC: 1953 AN: 68018

Other (OTH) AF: 0.112 AC: 237 AN: 2112

Alfa AF: 0.0316 Hom.: 51

Bravo AF: 0.151

Asia WGS AF: 0.0580 AC: 204 AN: 3478

EpiCase AF: 0.0327

EpiControl AF: 0.0303

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)
-	-	1	Pigmentary retinal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	9.9
DANN	Benign	0.79
PhyloP100		-0.94
Mutation Taster		=94/6	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13193; hg19: chr12-56117700;