chr1-205147743-C-A

Position:

• chr1-205147743-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015375.3(DSTYK):​c.2605G>T​(p.Ala869Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: DSTYK NM_015375.3 missense, splice_region
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 2.81

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.099720925).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSTYK	NM_015375.3	c.2605G>T	p.Ala869Ser	missense_variant, splice_region_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.2605G>T	p.Ala869Ser	missense_variant, splice_region_variant	13/13	1	NM_015375.3	ENSP00000356130	P1
DSTYK	ENST00000367161.7	c.2470G>T	p.Ala824Ser	missense_variant, splice_region_variant	12/12	1		ENSP00000356129

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Congenital anomalies of kidney and urinary tract 1 Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City

Feb 05, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	.;T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.018
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.80	T;D
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	.;N
MutationTaster	Benign	0.95	D;D;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.52	N;N
REVEL	Benign	0.029
Sift	Benign	0.56	T;T
Sift4G	Benign	0.64	T;T
Polyphen		0.0020	B;B
Vest4		0.035
MutPred		0.41		.;Gain of phosphorylation at A869 (P = 0.0127);
MVP		0.36
MPC		0.33
ClinPred		0.60	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.065
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: rs1574742379; hg19: chr1-205116871;