Genetic Variant NM_006205.3:c.*319T>C (chr12-14981795-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006205.3(PDE6H):c.*319T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00382 in 427,480 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 20 hom., cov: 32)

Exomes 𝑓: 0.0046 ( 40 hom. )

Consequence

PDE6H
NM_006205.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.760

Publications

0 publications found

Variant links:

Genes affected

PDE6H (HGNC:8790): (phosphodiesterase 6H) This gene encodes the inhibitory (or gamma) subunit of the cone-specific cGMP phosphodiesterase, which is a tetramer composed of two catalytic chains (alpha and beta), and two inhibitory chains (gamma). It is specifically expressed in the retina, and is involved in the transmission and amplification of the visual signal. Mutations in this gene are associated with retinal cone dystrophy type 3A (RCD3A). [provided by RefSeq, Mar 2010]

PDE6H Gene-Disease associations (from GenCC):

achromatopsia
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, G2P
retinal cone dystrophy 3A
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

PDE6H links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 12-14981795-T-C is Benign according to our data. Variant chr12-14981795-T-C is described in ClinVar as Benign. ClinVar VariationId is 307788.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.061 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006205.3. 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
	PDE6H	NM_006205.3	MANE Select	c.*319T>C		3_prime_UTR	Exon 4 of 4	NP_006196.1	Q13956

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE6H	ENST00000266395.3	TSL:1 MANE Select	c.*319T>C		3_prime_UTR	Exon 4 of 4	ENSP00000266395.2	Q13956
	PDE6H	ENST00000945511.1		c.*319T>C		3_prime_UTR	Exon 3 of 3	ENSP00000615570.1

Frequencies

GnomAD3 genomes

AF:

0.00249

AC:

379

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.0666

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00191

GnomAD4 exome

AF:

0.00456

AC:

1254

AN:

275170

Hom.:

Cov.:

AF XY:

0.00447

AC XY:

656

AN XY:

146714

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

8308

American (AMR)

AF:

0.0000896

AC:

AN:

11156

Ashkenazi Jewish (ASJ)

AF:

0.00134

AC:

AN:

8196

East Asian (EAS)

AF:

0.0721

AC:

1104

AN:

15312

South Asian (SAS)

AF:

0.00197

AC:

AN:

39142

European-Finnish (FIN)

AF:

0.0000742

AC:

AN:

13470

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1128

European-Non Finnish (NFE)

AF:

0.000104

AC:

AN:

163130

Other (OTH)

AF:

0.00267

AC:

AN:

15328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

114

170

227

284

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00249

AC:

380

AN:

152310

Hom.:

Cov.:

AF XY:

0.00302

AC XY:

225

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.000192

AC:

AN:

41568

American (AMR)

AF:

0.0000653

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3468

East Asian (EAS)

AF:

0.0668

AC:

346

AN:

5180

South Asian (SAS)

AF:

0.00207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68028

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00103

Hom.:

Bravo

AF:

0.00331

Asia WGS

AF:

0.0240

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Retinal cone dystrophy 3A (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.071

(source)

DANN

Benign

0.35

PhyloP100

-0.76

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over