rs714550

Variant names:

• chr10-93629284-G-A
• rs714550
• NM_006204.4:c.1098G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-93629284-G-A
• chr10-93629284-G-C
• chr10-93629284-G-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_006204.4(PDE6C):​c.1098G>A​(p.Ala366Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 1,603,472 control chromosomes in the GnomAD database, including 95,157 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (10476 hom., cov: 32)
  • Exomes 𝑓: 0.34 (84681 hom.)
• Consequence: PDE6C NM_006204.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.0920

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 Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 10-93629284-G-A is Benign according to our data. Variant chr10-93629284-G-A is described in ClinVar as [Benign]. Clinvar id is 259938.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-93629284-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.092 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE6C	NM_006204.4	c.1098G>A	p.Ala366Ala	synonymous_variant	Exon 8 of 22	ENST00000371447.4	NP_006195.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE6C	ENST00000371447.4	c.1098G>A	p.Ala366Ala	synonymous_variant	Exon 8 of 22	1	NM_006204.4	ENSP00000360502.3

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55760 AN: 151868 Hom.: 10454 Cov.: 32

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.350

GnomAD3 exomes AF: 0.353 AC: 88694 AN: 251332 Hom.: 16202 AF XY: 0.347 AC XY: 47106 AN XY: 135838

Gnomad AFR exome AF: 0.435

Gnomad AMR exome AF: 0.397

Gnomad ASJ exome AF: 0.326

Gnomad EAS exome AF: 0.459

Gnomad SAS exome AF: 0.305

Gnomad FIN exome AF: 0.329

Gnomad NFE exome AF: 0.332

Gnomad OTH exome AF: 0.329

GnomAD4 exome AF: 0.337 AC: 489322 AN: 1451486 Hom.: 84681 Cov.: 31 AF XY: 0.336 AC XY: 243104 AN XY: 722700

Gnomad4 AFR exome AF: 0.429

Gnomad4 AMR exome AF: 0.397

Gnomad4 ASJ exome AF: 0.323

Gnomad4 EAS exome AF: 0.466

Gnomad4 SAS exome AF: 0.306

Gnomad4 FIN exome AF: 0.327

Gnomad4 NFE exome AF: 0.330

Gnomad4 OTH exome AF: 0.352

GnomAD4 genome AF: 0.367 AC: 55831 AN: 151986 Hom.: 10476 Cov.: 32 AF XY: 0.366 AC XY: 27172 AN XY: 74278

Gnomad4 AFR AF: 0.429

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.465

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.352

Alfa AF: 0.337 Hom.: 11028

Bravo AF: 0.377

Asia WGS AF: 0.407 AC: 1415 AN: 3478

EpiCase AF: 0.338

EpiControl AF: 0.338

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Achromatopsia Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Cone dystrophy 4 Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	6.6
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs714550; hg19: chr10-95389041; COSMIC: COSV65115807;