1-186444239-C-T

Variant names:

• chr1-186444239-C-T
• NM_002597.5:c.481G>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002597.5(PDC):​c.481G>A​(p.Glu161Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDC NM_002597.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.65

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

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.888

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDC	NM_002597.5	c.481G>A	p.Glu161Lys	missense_variant	Exon 4 of 4	ENST00000391997.3	NP_002588.3
PDC	NM_022576.4	c.325G>A	p.Glu109Lys	missense_variant	Exon 3 of 3		NP_072098.1
PDC-AS1	NR_126002.1	n.346-6940C>T		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDC	ENST00000391997.3	c.481G>A	p.Glu161Lys	missense_variant	Exon 4 of 4	1	NM_002597.5	ENSP00000375855.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.481G>A (p.E161K) alteration is located in exon 4 (coding exon 3) of the PDC gene. This alteration results from a G to A substitution at nucleotide position 481, causing the glutamic acid (E) at amino acid position 161 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T;.
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.022	T
MetaRNN	Pathogenic	0.89	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.4	D;D
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	D;D
Sift4G	Benign	0.27	T;T
Polyphen		0.88	P;.
Vest4		0.58
MutPred		0.89		Loss of stability (P = 0.0802);.;
MVP		0.74
MPC		0.17
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.86
gMVP		0.75

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-186413371;