1-186443996-C-G

Variant names:

• chr1-186443996-C-G
• rs1378360955
• NM_002597.5:c.724G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002597.5(PDC):​c.724G>C​(p.Glu242Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000311 in 1,605,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: PDC NM_002597.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.46
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2390799).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDC	NM_002597.5	MANE Select	c.724G>C	p.Glu242Gln	missense	Exon 4 of 4	NP_002588.3
	PDC	NM_022576.4		c.568G>C	p.Glu190Gln	missense	Exon 3 of 3	NP_072098.1	P20941-2
	PDC-AS1	NR_126002.1		n.346-7183C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDC	ENST00000391997.3	TSL:1 MANE Select	c.724G>C	p.Glu242Gln	missense	Exon 4 of 4	ENSP00000375855.2	P20941-1
	PDC	ENST00000497198.1	TSL:1	c.568G>C	p.Glu190Gln	missense	Exon 3 of 3	ENSP00000422775.1	P20941-2
	PDC-AS1	ENST00000622121.1	TSL:4	n.346-7183C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152170 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000809 AC: 2 AN: 247198 AF XY: 0.00000749

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000297

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000167

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1453174 Hom.: 0 Cov.: 28 AF XY: 0.00000277 AC XY: 2 AN XY: 722944

African (AFR) AF: 0.00 AC: 0 AN: 33162

American (AMR) AF: 0.0000455 AC: 2 AN: 43944

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25860

East Asian (EAS) AF: 0.00 AC: 0 AN: 39628

South Asian (SAS) AF: 0.00 AC: 0 AN: 85326

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53302

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 9.04e-7 AC: 1 AN: 1106200

Other (OTH) AF: 0.0000167 AC: 1 AN: 60026

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152170 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74342

African (AFR) AF: 0.00 AC: 0 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		7.5
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.11
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.10	T
Polyphen		0.51	P
Vest4		0.18
MutPred		0.42		Loss of loop (P = 0.0374)
MVP		0.68
MPC		0.46
ClinPred		0.81	D
GERP RS		4.7
Varity_R		0.24
gMVP		0.55
Mutation Taster		=72/28	polymorphism

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: rs1378360955; hg19: chr1-186413128;