10-93621983-C-G

Position:

• chr10-93621983-C-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1 PM2 PP3_Moderate

The NM_006204.4(PDE6C):​c.775C>G​(p.Arg259Gly) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDE6C NM_006204.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.576

Genes affected

PDE6C (HGNC:8787): (phosphodiesterase 6C) This gene encodes the alpha-prime subunit of cone phosphodiesterase, which is composed of a homodimer of two alpha-prime subunits and 3 smaller proteins of 11, 13, and 15 kDa. Mutations in this gene are associated with cone dystrophy type 4 (COD4). [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM1: In a domain GAF 2 (size 177) in uniprot entity PDE6C_HUMAN there are 7 pathogenic changes around while only 0 benign (100%) in NM_006204.4
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.867

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE6C	NM_006204.4	c.775C>G	p.Arg259Gly	missense_variant	4/22	ENST00000371447.4	NP_006195.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE6C	ENST00000371447.4	c.775C>G	p.Arg259Gly	missense_variant	4/22	1	NM_006204.4	ENSP00000360502.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Uncertain	-0.064	T
MutationAssessor	Pathogenic	3.1	M
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Uncertain	0.52
Sift	Benign	0.12	T
Sift4G	Uncertain	0.053	T
Polyphen		1.0	D
Vest4		0.94
MutPred		0.46		Loss of MoRF binding (P = 0.0743);
MVP		0.86
MPC		1.0
ClinPred		0.99	D
GERP RS		1.8
Varity_R		0.46
gMVP		0.68

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

Other links and lift over

dbSNP: rs757622521; hg19: chr10-95381740;