5-149858701-C-T

Variant names:

• chr5-149858701-C-T
• rs30886
• NM_000440.3:c.*2194G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.736
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• PDE6A-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• retinitis pigmentosa 43

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000440.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE6A	NM_000440.3	MANE Select	c.*2194G>A		3_prime_UTR	Exon 22 of 22	NP_000431.2	P16499
	PDE6A	NM_001410788.1		c.*2194G>A		3_prime_UTR	Exon 20 of 20	NP_001397717.1	F1T0K3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE6A	ENST00000255266.10	TSL:1 MANE Select	c.*2194G>A		3_prime_UTR	Exon 22 of 22	ENSP00000255266.5	P16499
	PDE6A	ENST00000508173.5	TSL:1	n.4961G>A		non_coding_transcript_exon	Exon 20 of 20
	PDE6A	ENST00000613228.1	TSL:5	c.*2194G>A		3_prime_UTR	Exon 20 of 20	ENSP00000478060.1	F1T0K3

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68026 AN: 151658 Hom.: 15898 Cov.: 30

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: 58 AN: 110 Hom.: 17 Cov.: 0 AF XY: 0.547 AC XY: 47 AN XY: 86

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.333 AC: 2 AN: 6

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.543 AC: 51 AN: 94

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.448 AC: 68045 AN: 151776 Hom.: 15893 Cov.: 30 AF XY: 0.449 AC XY: 33325 AN XY: 74178

African (AFR) AF: 0.310 AC: 12821 AN: 41378

American (AMR) AF: 0.514 AC: 7839 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1538 AN: 3468

East Asian (EAS) AF: 0.513 AC: 2640 AN: 5146

South Asian (SAS) AF: 0.346 AC: 1664 AN: 4812

European-Finnish (FIN) AF: 0.468 AC: 4921 AN: 10506

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.516 AC: 35050 AN: 67904

Other (OTH) AF: 0.492 AC: 1035 AN: 2104

Alfa AF: 0.473 Hom.: 2152

Bravo AF: 0.445

Asia WGS AF: 0.414 AC: 1439 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.69
DANN	Benign	0.58
PhyloP100		-0.74
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs30886; hg19: chr5-149238264; COSMIC: COSV54925718; COSMIC: COSV54925718;