Variant chr1-205161285-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015375.3(DSTYK):c.1921T>C(p.Cys641Arg) variant causes a missense change. The variant allele was found at a frequency of 0.918 in 1,614,030 control chromosomes in the GnomAD database, including 680,196 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.94 ( 66715 hom., cov: 32)

Exomes 𝑓: 0.92 ( 613481 hom. )

Consequence

DSTYK
NM_015375.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 4.27

Variant links:

Genes affected

DSTYK (HGNC:29043): (dual serine/threonine and tyrosine protein kinase) This gene encodes a dual serine/threonine and tyrosine protein kinase which is expressed in multiple tissues. It is thought to function as a regulator of cell death. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

DSTYK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.123712E-7).

BP6

Variant 1-205161285-A-G is Benign according to our data. Variant chr1-205161285-A-G is described in ClinVar as [Benign]. Clinvar id is 260657.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSTYK	NM_015375.3 link	c.1921T>C	p.Cys641Arg	missense_variant	7/13	ENST00000367162.8	NP_056190.1	Q6XUX3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSTYK	ENST00000367162.8 link	c.1921T>C	p.Cys641Arg	missense_variant	7/13	1	NM_015375.3	ENSP00000356130.3		Q6XUX3-1
DSTYK	ENST00000367161.7 link	c.1921T>C	p.Cys641Arg	missense_variant	7/12	1		ENSP00000356129.3		Q6XUX3-2

Frequencies

GnomAD3 genomes

AF:

0.935

AC:

142314

AN:

152136

Hom.:

66655

Cov.:

show subpopulations

Gnomad AFR

AF:

0.984

Gnomad AMI

AF:

0.929

Gnomad AMR

AF:

0.940

Gnomad ASJ

AF:

0.917

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.951

Gnomad FIN

AF:

0.923

Gnomad MID

AF:

0.930

Gnomad NFE

AF:

0.902

Gnomad OTH

AF:

0.947

GnomAD3 exomes

AF:

0.932

AC:

233925

AN:

251116

Hom.:

109148

AF XY:

0.929

AC XY:

126007

AN XY:

135676

show subpopulations

Gnomad AFR exome

AF:

0.985

Gnomad AMR exome

AF:

0.963

Gnomad ASJ exome

AF:

0.906

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.946

Gnomad FIN exome

AF:

0.925

Gnomad NFE exome

AF:

0.903

Gnomad OTH exome

AF:

0.921

GnomAD4 exome

AF:

0.916

AC:

1338519

AN:

1461776

Hom.:

613481

Cov.:

AF XY:

0.915

AC XY:

665735

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.989

Gnomad4 AMR exome

AF:

0.964

Gnomad4 ASJ exome

AF:

0.904

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.943

Gnomad4 FIN exome

AF:

0.922

Gnomad4 NFE exome

AF:

0.906

Gnomad4 OTH exome

AF:

0.923

GnomAD4 genome

AF:

0.936

AC:

142434

AN:

152254

Hom.:

66715

Cov.:

AF XY:

0.936

AC XY:

69673

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.984

Gnomad4 AMR

AF:

0.940

Gnomad4 ASJ

AF:

0.917

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.951

Gnomad4 FIN

AF:

0.923

Gnomad4 NFE

AF:

0.902

Gnomad4 OTH

AF:

0.948

Alfa

AF:

0.910

Hom.:

161896

Bravo

AF:

0.941

TwinsUK

AF:

0.909

AC:

3372

ALSPAC

AF:

0.914

AC:

3521

ESP6500AA

AF:

0.980

AC:

4317

ESP6500EA

AF:

0.905

AC:

7781

ExAC

AF:

0.932

AC:

113112

Asia WGS

AF:

0.982

AC:

3417

AN:

3478

EpiCase

AF:

0.899

EpiControl

AF:

0.900

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	This variant is associated with the following publications: (PMID: 30389748) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Congenital anomalies of kidney and urinary tract 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Hereditary spastic paraplegia 23

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.045

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.55

DEOGEN2

Benign

0.00077

.;T;.

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.40

T;T;T

MetaRNN

Benign

9.1e-7

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.4

N;N;.

PrimateAI

Uncertain

0.78

PROVEAN

Benign

2.2

N;N;.

REVEL

Benign

0.21

Sift

Benign

0.57

T;T;.

Sift4G

Benign

0.18

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.26

MPC

0.64

ClinPred

0.0059

GERP RS

5.3

Varity_R

0.19

gMVP

0.72

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