1-205211450-C-A

Variant names:

• chr1-205211450-C-A
• NM_015375.3:c.86G>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_015375.3(DSTYK):​c.86G>T​(p.Arg29Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000691 in 1,446,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R29Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DSTYK NM_015375.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.21

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.817

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSTYK	NM_015375.3	c.86G>T	p.Arg29Leu	missense_variant	Exon 1 of 13	ENST00000367162.8	NP_056190.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSTYK	ENST00000367162.8	c.86G>T	p.Arg29Leu	missense_variant	Exon 1 of 13	1	NM_015375.3	ENSP00000356130.3
DSTYK	ENST00000367161.7	c.86G>T	p.Arg29Leu	missense_variant	Exon 1 of 12	1		ENSP00000356129.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1446952 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 719528

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: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.085	.;T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.84	T;T
M_CAP	Pathogenic	0.67	D
MetaRNN	Pathogenic	0.82	D;D
MetaSVM	Uncertain	0.35	D
MutationAssessor	Uncertain	2.0	M;M
PrimateAI	Pathogenic	0.92	D
PROVEAN	Uncertain	-2.5	D;D
REVEL	Pathogenic	0.65
Sift	Uncertain	0.013	D;D
Sift4G	Uncertain	0.035	D;D
Polyphen		1.0	D;D
Vest4		0.64
MutPred		0.46		Loss of loop (P = 0.0073);Loss of loop (P = 0.0073);
MVP		0.89
MPC		0.62
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.73
gMVP		0.62

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-205180578;