ENST00000549503.1:c.-45-17954A>G

Variant names:

• chr14-30065741-T-C
• rs225925
• ENST00000549503.1:c.-45-17954A>G

Variant summary

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

The ENST00000549503.1(PRKD1):​c.-45-17954A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.963 in 152,150 control chromosomes in the GnomAD database, including 70,597 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 0.96 (70597 hom., cov: 29)
• Consequence: PRKD1 ENST00000549503.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 1 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
• congenital heart disease

  Inheritance: AR, AD Classification: LIMITED Submitted by: ClinGen

ENSG00000248975 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 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.-45-17954A>G		intron	N/A	ENSP00000446866.1	F8VZ98
	ENSG00000248975	ENST00000549360.1	TSL:3	n.85-85474A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.963 AC: 146419 AN: 152032 Hom.: 70542 Cov.: 29

Gnomad AFR AF: 0.955

Gnomad AMI AF: 0.860

Gnomad AMR AF: 0.973

Gnomad ASJ AF: 0.969

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.916

Gnomad FIN AF: 0.986

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.964

Gnomad OTH AF: 0.966

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

GnomAD4 genome AF: 0.963 AC: 146534 AN: 152150 Hom.: 70597 Cov.: 29 AF XY: 0.963 AC XY: 71638 AN XY: 74374

African (AFR) AF: 0.955 AC: 39653 AN: 41514

American (AMR) AF: 0.973 AC: 14867 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.969 AC: 3364 AN: 3470

East Asian (EAS) AF: 0.998 AC: 5160 AN: 5168

South Asian (SAS) AF: 0.917 AC: 4407 AN: 4806

European-Finnish (FIN) AF: 0.986 AC: 10448 AN: 10600

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.964 AC: 65539 AN: 68002

Other (OTH) AF: 0.966 AC: 2036 AN: 2108

Alfa AF: 0.964 Hom.: 8066

Bravo AF: 0.963

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.90
DANN	Benign	0.26
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs225925; hg19: chr14-30534947;