chr1-205169835-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_015375.3(DSTYK):​c.655-3C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000225 in 1,605,724 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00024 ( 8 hom. )

Consequence

DSTYK
NM_015375.3 splice_region, intron

Scores

2
Splicing: ADA: 0.001592
2

Clinical Significance

Likely benign criteria provided, single submitter P:1B:1

Conservation

PhyloP100: 1.40
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
Variant 1-205169835-G-A is Benign according to our data. Variant chr1-205169835-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 60686.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000118 (18/152244) while in subpopulation SAS AF= 0.00352 (17/4824). AF 95% confidence interval is 0.00224. There are 0 homozygotes in gnomad4. There are 13 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 18 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DSTYKNM_015375.3 linkc.655-3C>T splice_region_variant, intron_variant ENST00000367162.8 NP_056190.1 Q6XUX3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DSTYKENST00000367162.8 linkc.655-3C>T splice_region_variant, intron_variant 1 NM_015375.3 ENSP00000356130.3 Q6XUX3-1
DSTYKENST00000367161.7 linkc.655-3C>T splice_region_variant, intron_variant 1 ENSP00000356129.3 Q6XUX3-2

Frequencies

GnomAD3 genomes
AF:
0.000118
AC:
18
AN:
152126
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00352
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000471
AC:
114
AN:
241984
Hom.:
1
AF XY:
0.000671
AC XY:
88
AN XY:
131198
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000547
Gnomad SAS exome
AF:
0.00374
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000916
Gnomad OTH exome
AF:
0.000170
GnomAD4 exome
AF:
0.000237
AC:
344
AN:
1453480
Hom.:
8
Cov.:
32
AF XY:
0.000353
AC XY:
255
AN XY:
722356
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000505
Gnomad4 SAS exome
AF:
0.00356
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000812
Gnomad4 OTH exome
AF:
0.000450
GnomAD4 genome
AF:
0.000118
AC:
18
AN:
152244
Hom.:
0
Cov.:
32
AF XY:
0.000175
AC XY:
13
AN XY:
74440
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00352
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000837
Hom.:
0
Bravo
AF:
0.0000378
Asia WGS
AF:
0.00231
AC:
8
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Pathogenic:1Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Congenital anomalies of kidney and urinary tract 1 Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMAug 15, 2013- -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpAug 24, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.40
CADD
Benign
11
DANN
Benign
0.79
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.0016
dbscSNV1_RF
Benign
0.044
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs554197975; hg19: chr1-205138963; API