Genetic Variant PDC:c.61+834A>G (chr1-186448565-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.61+834A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 283,448 control chromosomes in the GnomAD database, including 13,989 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 0.33 ( 9301 hom., cov: 32)

Exomes 𝑓: 0.26 ( 4688 hom. )

Consequence

PDC
NM_002597.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.50

Publications

4 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:

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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=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002597.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PDC	NM_002597.5	MANE Select	c.61+834A>G	intron	N/A	NP_002588.3
PDC	NM_022576.4		c.-96+63A>G	intron	N/A	NP_072098.1	P20941-2
PDC-AS1	NR_126002.1		n.346-2614T>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PDC	ENST00000391997.3	TSL:1 MANE Select	c.61+834A>G	intron	N/A	ENSP00000375855.2	P20941-1
PDC	ENST00000497198.1	TSL:1	c.-96+63A>G	intron	N/A	ENSP00000422775.1	P20941-2
PDC-AS1	ENST00000622121.1	TSL:4	n.346-2614T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.333

AC:

50533

AN:

151826

Hom.:

9258

Cov.:

show subpopulations

Gnomad AFR

AF:

0.479

Gnomad AMI

AF:

0.244

Gnomad AMR

AF:

0.372

Gnomad ASJ

AF:

0.316

Gnomad EAS

AF:

0.426

Gnomad SAS

AF:

0.258

Gnomad FIN

AF:

0.217

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.253

Gnomad OTH

AF:

0.344

GnomAD4 exome

AF:

0.263

AC:

34542

AN:

131502

Hom.:

4688

AF XY:

0.262

AC XY:

16671

AN XY:

63700

show subpopulations

African (AFR)

AF:

0.507

AC:

1209

AN:

2384

American (AMR)

AF:

0.384

AC:

AN:

146

Ashkenazi Jewish (ASJ)

AF:

0.308

AC:

259

AN:

840

East Asian (EAS)

AF:

0.442

AC:

242

AN:

548

South Asian (SAS)

AF:

0.262

AC:

668

AN:

2552

European-Finnish (FIN)

AF:

0.263

AC:

AN:

Middle Eastern (MID)

AF:

0.292

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.256

AC:

30807

AN:

120436

Other (OTH)

AF:

0.283

AC:

1221

AN:

4318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1309

2618

3926

5235

6544

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1442

2884

4326

5768

7210

<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:

0.333

AC:

50622

AN:

151946

Hom.:

9301

Cov.:

AF XY:

0.333

AC XY:

24722

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.480

AC:

19867

AN:

41412

American (AMR)

AF:

0.373

AC:

5698

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.316

AC:

1094

AN:

3464

East Asian (EAS)

AF:

0.425

AC:

2197

AN:

5166

South Asian (SAS)

AF:

0.256

AC:

1236

AN:

4822

European-Finnish (FIN)

AF:

0.217

AC:

2298

AN:

10570

Middle Eastern (MID)

AF:

0.272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.253

AC:

17195

AN:

67934

Other (OTH)

AF:

0.348

AC:

735

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1657

3315

4972

6630

8287

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

490

980

1470

1960

2450

<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:

0.185

Hom.:

482

Bravo

AF:

0.358

Asia WGS

AF:

0.396

AC:

1375

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.41

(source)

DANN

Benign

0.42

PhyloP100

-1.5

PromoterAI

0.0068

Neutral

(source)

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over