Genetic Variant PRKD1:c.-46+32315G>C (chr14-30158984-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000549503.1(PRKD1):c.-46+32315G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0257 in 152,162 control chromosomes in the GnomAD database, including 87 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 0.026 ( 87 hom., cov: 32)

Consequence

PRKD1
ENST00000549503.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.487

Publications

2 publications found

Variant links:

Genes affected

PRKD1 (HGNC:9407): (protein kinase D1) The protein encoded by this gene is a serine/threonine protein kinase involved in many cellular processes, including Golgi body membrane integrity and transport, cell migration and differentiation, MAPK8/JNK1 and Ras pathway signaling, MAPK1/3 (ERK1/2) pathway signaling, cell survival, and regulation of cell shape and adhesion. [provided by RefSeq, Jan 2017]

PRKD1 Gene-Disease associations (from GenCC):

congenital heart defects and ectodermal dysplasia
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
congenital heart defects, multiple types
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
complex neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
congenital heart disease
Inheritance: AD, AR Classification: LIMITED Submitted by: ClinGen

PRKD1 links:

ENSG00000248975 (HGNC:):

ENSG00000248975 links:

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new If you want to explore the variant's impact on the transcript ENST00000549503.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0581 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000549503.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKD1	ENST00000549503.1	TSL:3	c.-46+32315G>C		intron	N/A	ENSP00000446866.1	F8VZ98
	ENSG00000248975	ENST00000549360.1	TSL:3	n.84+137950G>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0257

AC:

3904

AN:

152044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0600

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0211

Gnomad ASJ

AF:

0.00980

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00374

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0143

Gnomad OTH

AF:

0.0192

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

GnomAD4 genome

AF:

0.0257

AC:

3917

AN:

152162

Hom.:

Cov.:

AF XY:

0.0245

AC XY:

1826

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.0601

AC:

2495

AN:

41528

American (AMR)

AF:

0.0210

AC:

321

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00980

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5170

South Asian (SAS)

AF:

0.00374

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00113

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0143

AC:

972

AN:

67992

Other (OTH)

AF:

0.0190

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

195

390

586

781

976

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<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:

0.0179

Hom.:

Bravo

AF:

0.0285

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.6

(source)

DANN

Benign

0.33

PhyloP100

0.49

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over