Variant chr14-29577305-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_002742.3(PRKD1):c.2672A>G(p.His891Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,613,844 control chromosomes in the GnomAD database, including 144 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.011 ( 28 hom., cov: 32)

Exomes 𝑓: 0.011 ( 116 hom. )

Consequence

PRKD1
NM_002742.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.66

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029675663).

BP6

Variant 14-29577305-T-C is Benign according to our data. Variant chr14-29577305-T-C is described in ClinVar as [Benign]. Clinvar id is 2644146.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0106 (15553/1461588) while in subpopulation MID AF= 0.0209 (120/5750). AF 95% confidence interval is 0.0178. There are 116 homozygotes in gnomad4_exome. There are 7726 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1697 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKD1	NM_002742.3 linkuse as main transcript	c.2672A>G	p.His891Arg	missense_variant	18/18	ENST00000331968.11	NP_002733.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKD1	ENST00000331968.11 linkuse as main transcript	c.2672A>G	p.His891Arg	missense_variant	18/18	1	NM_002742.3	ENSP00000333568	P3

Frequencies

GnomAD3 genomes

AF:

0.0112

AC:

1697

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00183

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0115

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00455

Gnomad FIN

AF:

0.0470

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0126

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.0120

AC:

3013

AN:

250974

Hom.:

AF XY:

0.0125

AC XY:

1699

AN XY:

135596

show subpopulations

Gnomad AFR exome

AF:

0.00191

Gnomad AMR exome

AF:

0.00683

Gnomad ASJ exome

AF:

0.00457

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00349

Gnomad FIN exome

AF:

0.0442

Gnomad NFE exome

AF:

0.0138

Gnomad OTH exome

AF:

0.0119

GnomAD4 exome

AF:

0.0106

AC:

15553

AN:

1461588

Hom.:

116

Cov.:

AF XY:

0.0106

AC XY:

7726

AN XY:

727098

show subpopulations

Gnomad4 AFR exome

AF:

0.00194

Gnomad4 AMR exome

AF:

0.00682

Gnomad4 ASJ exome

AF:

0.00540

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00349

Gnomad4 FIN exome

AF:

0.0414

Gnomad4 NFE exome

AF:

0.0106

Gnomad4 OTH exome

AF:

0.0107

GnomAD4 genome

AF:

0.0111

AC:

1697

AN:

152256

Hom.:

Cov.:

AF XY:

0.0123

AC XY:

912

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00183

Gnomad4 AMR

AF:

0.0115

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00456

Gnomad4 FIN

AF:

0.0470

Gnomad4 NFE

AF:

0.0126

Gnomad4 OTH

AF:

0.0152

Alfa

AF:

0.0117

Hom.:

Bravo

AF:

0.00811

TwinsUK

AF:

0.0111

AC:

ALSPAC

AF:

0.0104

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.0133

AC:

114

ExAC

AF:

0.0112

AC:

1362

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0134

EpiControl

AF:

0.0134

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

PRKD1: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.18

T;T;T

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.63

T;.;T

MetaRNN

Benign

0.0030

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.41

N;N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.49

.;N;N

REVEL

Benign

0.050

Sift

Benign

0.38

.;T;T

Sift4G

Benign

0.44

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.089

MPC

0.42

ClinPred

0.0095

GERP RS

3.5

Varity_R

0.082

gMVP

0.41

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over