1-205147586-G-C

Position:

• chr1-205147586-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_015375.3(DSTYK):​c.2762C>G​(p.Pro921Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000822 in 1,459,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: DSTYK NM_015375.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.53

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.050990343).
• BS2: High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSTYK	NM_015375.3	c.2762C>G	p.Pro921Arg	missense_variant	13/13	ENST00000367162.8	NP_056190.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSTYK	ENST00000367162.8	c.2762C>G	p.Pro921Arg	missense_variant	13/13	1	NM_015375.3	ENSP00000356130.3
DSTYK	ENST00000367161.7	c.2627C>G	p.Pro876Arg	missense_variant	12/12	1		ENSP00000356129.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000797 AC: 2 AN: 250920 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135578

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000822 AC: 12 AN: 1459908 Hom.: 0 Cov.: 31 AF XY: 0.00000551 AC XY: 4 AN XY: 725788

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000108

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2024

DSTYK: PM2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Benign	0.89
DEOGEN2	Benign	0.0063	.;T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.051	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.0	.;L
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.50	N;N
REVEL	Benign	0.070
Sift	Benign	0.61	T;T
Sift4G	Benign	0.63	T;T
Polyphen		0.0010	B;B
Vest4		0.063
MutPred		0.34		.;Gain of MoRF binding (P = 0.0269);
MVP		0.34
MPC		0.38
ClinPred		0.055	T
GERP RS		3.2
Varity_R		0.030
gMVP		0.42

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

Other links and lift over

dbSNP: rs1411730987; hg19: chr1-205116714;