chr5-149858233-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000440.3(PDE6A):​c.*2662A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00744 in 152,336 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0074 ( 14 hom., cov: 32)
Failed GnomAD Quality Control

Consequence

PDE6A
NM_000440.3 3_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.33
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
Variant 5-149858233-T-C is Benign according to our data. Variant chr5-149858233-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 351940.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00744 (1134/152336) while in subpopulation AFR AF= 0.026 (1081/41568). AF 95% confidence interval is 0.0247. There are 14 homozygotes in gnomad4. There are 521 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PDE6ANM_000440.3 linkuse as main transcriptc.*2662A>G 3_prime_UTR_variant 22/22 ENST00000255266.10
PDE6ANM_001410788.1 linkuse as main transcriptc.*2662A>G 3_prime_UTR_variant 20/20

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PDE6AENST00000255266.10 linkuse as main transcriptc.*2662A>G 3_prime_UTR_variant 22/221 NM_000440.3 P1
PDE6AENST00000508173.5 linkuse as main transcriptn.5429A>G non_coding_transcript_exon_variant 20/201
PDE6AENST00000613228.1 linkuse as main transcriptc.*2662A>G 3_prime_UTR_variant 20/205

Frequencies

GnomAD3 genomes
AF:
0.00733
AC:
1116
AN:
152218
Hom.:
12
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0256
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00229
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000415
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00478
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AC:
0
AN:
0
Hom.:
0
Cov.:
0
AC XY:
0
AN XY:
0
GnomAD4 genome
AF:
0.00744
AC:
1134
AN:
152336
Hom.:
14
Cov.:
32
AF XY:
0.00699
AC XY:
521
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.0260
Gnomad4 AMR
AF:
0.00229
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00473
Alfa
AF:
0.00769
Hom.:
4
Bravo
AF:
0.00815
Asia WGS
AF:
0.00231
AC:
8
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Retinitis pigmentosa Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
6.2
DANN
Benign
0.57

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.

Other links and lift over

dbSNP: rs150127383; hg19: chr5-149237796; API