10-93632828-G-C

Variant names:

• chr10-93632828-G-C
• rs640090
• NM_006204.4:c.1120-1930G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006204.4(PDE6C):​c.1120-1930G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.882 in 152,232 control chromosomes in the GnomAD database, including 60,953 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.88 (60953 hom., cov: 33)
• Consequence: PDE6C NM_006204.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129
• Publications: 2 publications found

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]

PDE6C Gene-Disease associations (from GenCC):

• cone dystrophy 4

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• PDE6C-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• cone dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• achromatopsia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006204.4. 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
	PDE6C	NM_006204.4	MANE Select	c.1120-1930G>C		intron	N/A	NP_006195.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE6C	ENST00000371447.4	TSL:1 MANE Select	c.1120-1930G>C		intron	N/A	ENSP00000360502.3	P51160

Frequencies

GnomAD3 genomes AF: 0.883 AC: 134247 AN: 152114 Hom.: 60933 Cov.: 33

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.973

Gnomad AMR AF: 0.938

Gnomad ASJ AF: 0.990

Gnomad EAS AF: 0.959

Gnomad SAS AF: 0.950

Gnomad FIN AF: 0.996

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.980

Gnomad OTH AF: 0.915

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.882 AC: 134310 AN: 152232 Hom.: 60953 Cov.: 33 AF XY: 0.886 AC XY: 65934 AN XY: 74420

African (AFR) AF: 0.642 AC: 26648 AN: 41488

American (AMR) AF: 0.938 AC: 14353 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.990 AC: 3439 AN: 3472

East Asian (EAS) AF: 0.959 AC: 4961 AN: 5172

South Asian (SAS) AF: 0.950 AC: 4590 AN: 4832

European-Finnish (FIN) AF: 0.996 AC: 10572 AN: 10618

Middle Eastern (MID) AF: 0.921 AC: 269 AN: 292

European-Non Finnish (NFE) AF: 0.980 AC: 66659 AN: 68034

Other (OTH) AF: 0.915 AC: 1932 AN: 2112

Alfa AF: 0.925 Hom.: 8231

Bravo AF: 0.868

Asia WGS AF: 0.930 AC: 3232 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.22
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

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: rs640090; hg19: chr10-95392585;