chr1-186444312-A-C

Position:

• chr1-186444312-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002597.5(PDC):​c.408T>G​(p.Ile136Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign 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: -0.259

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34593165).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDC	NM_002597.5	c.408T>G	p.Ile136Met	missense_variant	4/4	ENST00000391997.3
PDC-AS1	NR_126002.1	n.346-6867A>C		intron_variant, non_coding_transcript_variant
PDC	NM_022576.4	c.252T>G	p.Ile84Met	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDC	ENST00000391997.3	c.408T>G	p.Ile136Met	missense_variant	4/4	1	NM_002597.5	P1

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 08, 2024

The c.408T>G (p.I136M) alteration is located in exon 4 (coding exon 3) of the PDC gene. This alteration results from a T to G substitution at nucleotide position 408, causing the isoleucine (I) at amino acid position 136 to be replaced by a methionine (M). 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	0.20
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	6.5
DANN	Benign	0.87
DEOGEN2	Uncertain	0.48	T;.
Eigen	Benign	-0.93
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.25	N
LIST_S2	Pathogenic	0.99	D;D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;.
MutationTaster	Benign	0.74	D;D;D;D
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.28
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.87	P;.
Vest4		0.42
MutPred		0.81		Loss of sheet (P = 0.0817);.;
MVP		0.26
MPC		0.52
ClinPred		0.93	D
GERP RS		-3.2
Varity_R		0.61
gMVP		0.71

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: chr1-186413444;