rs10505784

chr12-14974207-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006205.3(PDE6H):c.-42+1121A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,252 control chromosomes in the GnomAD database, including 1,162 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (1162 hom., cov: 33)
• Consequence: PDE6H NM_006205.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.125

Genes affected

PDE6H (HGNC:8790): (phosphodiesterase 6H) This gene encodes the inhibitory (or gamma) subunit of the cone-specific cGMP phosphodiesterase, which is a tetramer composed of two catalytic chains (alpha and beta), and two inhibitory chains (gamma). It is specifically expressed in the retina, and is involved in the transmission and amplification of the visual signal. Mutations in this gene are associated with retinal cone dystrophy type 3A (RCD3A). [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE6H	NM_006205.3	c.-42+1121A>G		intron_variant		ENST00000266395.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE6H	ENST00000266395.3	c.-42+1121A>G		intron_variant		1	NM_006205.3	P1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17844 AN: 152132 Hom.: 1161 Cov.: 33

Gnomad AFR AF: 0.0975

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.0939

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.134

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.117 AC: 17845 AN: 152252 Hom.: 1162 Cov.: 33 AF XY: 0.119 AC XY: 8859 AN XY: 74446

Gnomad4 AFR AF: 0.0973

Gnomad4 AMR AF: 0.0938

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.132

Alfa AF: 0.125 Hom.: 1711

Bravo AF: 0.111

Asia WGS AF: 0.172 AC: 600 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	5.2
Dann	Benign	0.52

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

Other links and lift over

dbSNP: rs10505784; hg19: chr12-15127141;