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. The variant received -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
• Publications: 18 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 -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 VariationId is 259938.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

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.1098G>A	p.Ala366Ala	synonymous	Exon 8 of 22	NP_006195.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE6C	ENST00000371447.4	TSL:1 MANE Select	c.1098G>A	p.Ala366Ala	synonymous	Exon 8 of 22	ENSP00000360502.3	P51160

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

GnomAD2 exomes AF: 0.353 AC: 88694 AN: 251332 AF XY: 0.347

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 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

African (AFR) AF: 0.429 AC: 14252 AN: 33250

American (AMR) AF: 0.397 AC: 17765 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 8430 AN: 26080

East Asian (EAS) AF: 0.466 AC: 18475 AN: 39626

South Asian (SAS) AF: 0.306 AC: 26363 AN: 86018

European-Finnish (FIN) AF: 0.327 AC: 17464 AN: 53388

Middle Eastern (MID) AF: 0.333 AC: 1918 AN: 5752

European-Non Finnish (NFE) AF: 0.330 AC: 363530 AN: 1102658

Other (OTH) AF: 0.352 AC: 21125 AN: 60014

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

African (AFR) AF: 0.429 AC: 17771 AN: 41450

American (AMR) AF: 0.385 AC: 5876 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1092 AN: 3468

East Asian (EAS) AF: 0.465 AC: 2399 AN: 5154

South Asian (SAS) AF: 0.302 AC: 1454 AN: 4812

European-Finnish (FIN) AF: 0.322 AC: 3400 AN: 10552

Middle Eastern (MID) AF: 0.315 AC: 92 AN: 292

European-Non Finnish (NFE) AF: 0.333 AC: 22614 AN: 67958

Other (OTH) AF: 0.352 AC: 743 AN: 2110

Alfa AF: 0.341 Hom.: 14107

Bravo AF: 0.377

Asia WGS AF: 0.407 AC: 1415 AN: 3478

EpiCase AF: 0.338

EpiControl AF: 0.338

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	1	Achromatopsia (1)
-	-	1	Cone dystrophy 4 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	6.6
DANN	Benign	0.70
PhyloP100		0.092
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs714550; hg19: chr10-95389041; COSMIC: COSV65115807;