rs11056264

chr12-14973069-G-Cchr12-14973069-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006205.3(PDE6H):c.-59G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,166 control chromosomes in the GnomAD database, including 1,167 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1167 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDE6H NM_006205.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 12-14973069-G-C is Benign according to our data. Variant chr12-14973069-G-C is described in ClinVar as [Benign]. Clinvar id is 307780.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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.-59G>C		5_prime_UTR_variant	1/4	ENST00000266395.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE6H	ENST00000266395.3	c.-59G>C		5_prime_UTR_variant	1/4	1	NM_006205.3	P1

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17920 AN: 152048 Hom.: 1166 Cov.: 32

Gnomad AFR AF: 0.0999

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.0937

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.134

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 12 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 10

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.118 AC: 17921 AN: 152166 Hom.: 1167 Cov.: 32 AF XY: 0.119 AC XY: 8882 AN XY: 74376

Gnomad4 AFR AF: 0.0997

Gnomad4 AMR AF: 0.0936

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.101

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.131

Alfa AF: 0.0594 Hom.: 63

Bravo AF: 0.112

Asia WGS AF: 0.171 AC: 596 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Retinal cone dystrophy 3A Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	3.5
Dann	Benign	0.56

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: rs11056264; hg19: chr12-15126003;