Genetic Variant NM_002597.5:c.*390A>G (chr1-186443589-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002597.5(PDC):c.*390A>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 0.202 in 158,250 control chromosomes in the GnomAD database, including 4,663 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 0.20 ( 4571 hom., cov: 32)

Exomes 𝑓: 0.14 ( 92 hom. )

Consequence

PDC
NM_002597.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0310

Publications

3 publications found

Variant links:

Genes affected

PDC (HGNC:8759): (phosducin) This gene encodes a phosphoprotein, which is located in the outer and inner segments of the rod cells in the retina. This protein may participate in the regulation of visual phototransduction or in the integration of photoreceptor metabolism. It modulates the phototransduction cascade by interacting with the beta and gamma subunits of the retinal G-protein transducin. This gene is a potential candidate gene for retinitis pigmentosa and Usher syndrome type II. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

PDC links:

PDC-AS1 (HGNC:40432): (PDC antisense RNA 1)

PDC-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PDC	NM_002597.5 link	c.*390A>G	3_prime_UTR_variant	Exon 4 of 4	ENST00000391997.3	NP_002588.3	P20941-1Q52LP8
PDC	NM_022576.4 link	c.*390A>G	3_prime_UTR_variant	Exon 3 of 3		NP_072098.1	P20941-2A0A024R982
PDC-AS1	NR_126002.1 link	n.345+7016T>C	intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDC	ENST00000391997.3 link	c.*390A>G		3_prime_UTR_variant	Exon 4 of 4	1	NM_002597.5	ENSP00000375855.2		P20941-1

Frequencies

GnomAD3 genomes

AF:

0.204

AC:

30994

AN:

151960

Hom.:

4547

Cov.:

show subpopulations

Gnomad AFR

AF:

0.414

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.157

Gnomad ASJ

AF:

0.217

Gnomad EAS

AF:

0.0405

Gnomad SAS

AF:

0.119

Gnomad FIN

AF:

0.0680

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.128

Gnomad OTH

AF:

0.198

GnomAD4 exome

AF:

0.141

AC:

870

AN:

6172

Hom.:

Cov.:

AF XY:

0.142

AC XY:

451

AN XY:

3172

show subpopulations

African (AFR)

AF:

0.373

AC:

AN:

166

American (AMR)

AF:

0.171

AC:

110

AN:

644

Ashkenazi Jewish (ASJ)

AF:

0.263

AC:

AN:

160

East Asian (EAS)

AF:

0.0451

AC:

AN:

244

South Asian (SAS)

AF:

0.133

AC:

AN:

332

European-Finnish (FIN)

AF:

0.0942

AC:

AN:

138

Middle Eastern (MID)

AF:

0.125

AC:

AN:

European-Non Finnish (NFE)

AF:

0.129

AC:

541

AN:

4184

Other (OTH)

AF:

0.156

AC:

AN:

288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

104

138

173

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.204

AC:

31059

AN:

152078

Hom.:

4571

Cov.:

AF XY:

0.198

AC XY:

14735

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.414

AC:

17181

AN:

41458

American (AMR)

AF:

0.157

AC:

2402

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.217

AC:

751

AN:

3466

East Asian (EAS)

AF:

0.0402

AC:

208

AN:

5176

South Asian (SAS)

AF:

0.119

AC:

572

AN:

4818

European-Finnish (FIN)

AF:

0.0680

AC:

720

AN:

10596

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.128

AC:

8718

AN:

67972

Other (OTH)

AF:

0.201

AC:

425

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1128

2256

3383

4511

5639

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

310

620

930

1240

1550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.175

Hom.:

1052

Bravo

AF:

0.222

Asia WGS

AF:

0.134

AC:

464

AN:

3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

9.2

(source)

DANN

Benign

0.86

PhyloP100

-0.031

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over