ENST00000549503.1:c.33+118040T>C

Variant names:

• chr14-29929670-A-G
• rs10498313
• ENST00000549503.1:c.33+118040T>C

Variant summary

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

The ENST00000549503.1(PRKD1):​c.33+118040T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,116 control chromosomes in the GnomAD database, including 2,813 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 0.19 (2813 hom., cov: 32)
• Consequence: PRKD1 ENST00000549503.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.417
• Publications: 3 publications found

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

ENSG00000287142 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.21 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKD1	ENST00000549503.1	TSL:3	c.33+118040T>C		intron	N/A	ENSP00000446866.1
	ENSG00000287142	ENST00000654897.1		n.667+559A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28368 AN: 151998 Hom.: 2811 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.187 AC: 28396 AN: 152116 Hom.: 2813 Cov.: 32 AF XY: 0.185 AC XY: 13728 AN XY: 74358

African (AFR) AF: 0.146 AC: 6038 AN: 41482

American (AMR) AF: 0.205 AC: 3139 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 780 AN: 3472

East Asian (EAS) AF: 0.164 AC: 847 AN: 5170

South Asian (SAS) AF: 0.180 AC: 870 AN: 4826

European-Finnish (FIN) AF: 0.138 AC: 1463 AN: 10570

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14465 AN: 67986

Other (OTH) AF: 0.212 AC: 448 AN: 2112

Alfa AF: 0.197 Hom.: 3380

Bravo AF: 0.188

Asia WGS AF: 0.173 AC: 601 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.4
DANN	Benign	0.57
PhyloP100		0.42

Splicing

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

Other links and lift over

dbSNP: rs10498313; hg19: chr14-30398876;