dbSNP rs141951413: PDC:p.Asp86Glu (chr1-186444462-A-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_002597.5(PDC):c.258T>G(p.Asp86Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,456,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D86D) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PDC
NM_002597.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.77

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 made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.795

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDC	NM_002597.5 link	c.258T>G	p.Asp86Glu	missense_variant	Exon 4 of 4	ENST00000391997.3	NP_002588.3	P20941-1Q52LP8
PDC	NM_022576.4 link	c.102T>G	p.Asp34Glu	missense_variant	Exon 3 of 3		NP_072098.1	P20941-2A0A024R982
PDC-AS1	NR_126002.1 link	n.346-6717A>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.258T>G	p.Asp86Glu	missense_variant	Exon 4 of 4	1	NM_002597.5	ENSP00000375855.2		P20941-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249642

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

134878

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1456854

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725110

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Uncertain

0.069

BayesDel_noAF

Uncertain

-0.040

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.43

T;.

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.031

MetaRNN

Pathogenic

0.79

D;D

MetaSVM

Benign

-0.64

MutationAssessor

Uncertain

2.6

M;.

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-2.3

N;N

REVEL

Uncertain

0.39

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.13

T;T

Polyphen

0.97

D;.

Vest4

0.72

MutPred

0.64

Loss of helix (P = 0.0444);.;

MVP

0.66

MPC

0.40

ClinPred

0.94

GERP RS

3.2

Varity_R

0.49

gMVP

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over