1-205161285-A-T

Position:

• chr1-205161285-A-T

Variant summary

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

The NM_015375.3(DSTYK):​c.1921T>A​(p.Cys641Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C641R) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DSTYK NM_015375.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.27

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=0.12681466).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSTYK	NM_015375.3	c.1921T>A	p.Cys641Ser	missense_variant	7/13	ENST00000367162.8	NP_056190.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSTYK	ENST00000367162.8	c.1921T>A	p.Cys641Ser	missense_variant	7/13	1	NM_015375.3	ENSP00000356130.3
DSTYK	ENST00000367161.7	c.1921T>A	p.Cys641Ser	missense_variant	7/12	1		ENSP00000356129.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461826 Hom.: 0 Cov.: 53 AF XY: 0.00 AC XY: 0 AN XY: 727212

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	20
DANN	Benign	0.83
DEOGEN2	Benign	0.00084	.;T;.
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.82	T;T;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.0	N;N;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	1.4	N;N;.
REVEL	Benign	0.21
Sift	Benign	0.33	T;T;.
Sift4G	Benign	0.75	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.31
MutPred		0.52		Gain of disorder (P = 7e-04);Gain of disorder (P = 7e-04);.;
MVP		0.38
MPC		0.44
ClinPred		0.57	D
GERP RS		5.3
Varity_R		0.081
gMVP		0.75

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: rs3851294; hg19: chr1-205130413;