Variant 5-149858701-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000440.3(PDE6A):c.*2194G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 151,886 control chromosomes in the GnomAD database, including 15,910 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.45 ( 15893 hom., cov: 30)

Exomes 𝑓: 0.53 ( 17 hom. )

Consequence

PDE6A
NM_000440.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.736

Variant links:

Genes affected

PDE6A (HGNC:8785): (phosphodiesterase 6A) This gene encodes the cyclic-GMP (cGMP)-specific phosphodiesterase 6A alpha subunit, expressed in cells of the retinal rod outer segment. The phosphodiesterase 6 holoenzyme is a heterotrimer composed of an alpha, beta, and two gamma subunits. cGMP is an important regulator of rod cell membrane current, and its dynamic concentration is established by phosphodiesterase 6A cGMP hydrolysis and guanylate cyclase cGMP synthesis. The protein is a subunit of a key phototransduction enzyme and participates in processes of transmission and amplification of the visual signal. Mutations in this gene have been identified as one cause of autosomal recessive retinitis pigmentosa. [provided by RefSeq, Jul 2008]

PDE6A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BP6

Variant 5-149858701-C-T is Benign according to our data. Variant chr5-149858701-C-T is described in ClinVar as [Benign]. Clinvar id is 351947.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE6A	NM_000440.3 linkuse as main transcript	c.*2194G>A		3_prime_UTR_variant	22/22	ENST00000255266.10	NP_000431.2
PDE6A	NM_001410788.1 linkuse as main transcript	c.*2194G>A		3_prime_UTR_variant	20/20		NP_001397717.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
PDE6A	ENST00000255266.10 linkuse as main transcript	c.*2194G>A	3_prime_UTR_variant	22/22	1	NM_000440.3	ENSP00000255266	P1
PDE6A	ENST00000508173.5 linkuse as main transcript	n.4961G>A	non_coding_transcript_exon_variant	20/20	1
PDE6A	ENST00000613228.1 linkuse as main transcript	c.*2194G>A	3_prime_UTR_variant	20/20	5		ENSP00000478060

Frequencies

GnomAD3 genomes

AF:

0.449

AC:

68026

AN:

151658

Hom.:

15898

Cov.:

show subpopulations

Gnomad AFR

AF:

0.310

Gnomad AMI

AF:

0.425

Gnomad AMR

AF:

0.514

Gnomad ASJ

AF:

0.443

Gnomad EAS

AF:

0.513

Gnomad SAS

AF:

0.345

Gnomad FIN

AF:

0.468

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.516

Gnomad OTH

AF:

0.494

GnomAD4 exome

AF:

0.527

AC:

AN:

110

Hom.:

Cov.:

AF XY:

0.547

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

0.500

Gnomad4 SAS exome

AF:

0.333

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.543

Gnomad4 OTH exome

AF:

0.500

GnomAD4 genome

AF:

0.448

AC:

68045

AN:

151776

Hom.:

15893

Cov.:

AF XY:

0.449

AC XY:

33325

AN XY:

74178

show subpopulations

Gnomad4 AFR

AF:

0.310

Gnomad4 AMR

AF:

0.514

Gnomad4 ASJ

AF:

0.443

Gnomad4 EAS

AF:

0.513

Gnomad4 SAS

AF:

0.346

Gnomad4 FIN

AF:

0.468

Gnomad4 NFE

AF:

0.516

Gnomad4 OTH

AF:

0.492

Alfa

AF:

0.473

Hom.:

2152

Bravo

AF:

0.445

Asia WGS

AF:

0.414

AC:

1439

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Retinitis pigmentosa

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

-0.99

CADD

Benign

0.69

DANN

Benign

0.58

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over