rs3851294

Variant names:

• chr1-205161285-A-G
• rs3851294
• NM_015375.3:c.1921T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-205161285-A-G
• chr1-205161285-A-C
• chr1-205161285-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015375.3(DSTYK):​c.1921T>C​(p.Cys641Arg) variant causes a missense change. The variant allele was found at a frequency of 0.918 in 1,614,030 control chromosomes in the GnomAD database, including 680,196 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.94 (66715 hom., cov: 32)
  • Exomes 𝑓: 0.92 (613481 hom.)
• Consequence: DSTYK NM_015375.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 4.27
• Publications: 55 publications found

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]

DSTYK Gene-Disease associations (from GenCC):

• congenital anomalies of kidney and urinary tract 1

  Inheritance: AD, AR Classification: DEFINITIVE, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hereditary spastic paraplegia 23

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, G2P
• complex hereditary spastic paraplegia

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• renal agenesis, unilateral

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.123712E-7).
• BP6: Variant 1-205161285-A-G is Benign according to our data. Variant chr1-205161285-A-G is described in ClinVar as Benign. ClinVar VariationId is 260657.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015375.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSTYK	NM_015375.3	MANE Select	c.1921T>C	p.Cys641Arg	missense	Exon 7 of 13	NP_056190.1	Q6XUX3-1
	DSTYK	NM_199462.3		c.1921T>C	p.Cys641Arg	missense	Exon 7 of 12	NP_955749.1	Q6XUX3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSTYK	ENST00000367162.8	TSL:1 MANE Select	c.1921T>C	p.Cys641Arg	missense	Exon 7 of 13	ENSP00000356130.3	Q6XUX3-1
	DSTYK	ENST00000367161.7	TSL:1	c.1921T>C	p.Cys641Arg	missense	Exon 7 of 12	ENSP00000356129.3	Q6XUX3-2
	DSTYK	ENST00000893236.1		c.1894T>C	p.Cys632Arg	missense	Exon 7 of 13	ENSP00000563295.1

Frequencies

GnomAD3 genomes AF: 0.935 AC: 142314 AN: 152136 Hom.: 66655 Cov.: 32

Gnomad AFR AF: 0.984

Gnomad AMI AF: 0.929

Gnomad AMR AF: 0.940

Gnomad ASJ AF: 0.917

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.951

Gnomad FIN AF: 0.923

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.902

Gnomad OTH AF: 0.947

GnomAD2 exomes AF: 0.932 AC: 233925 AN: 251116 AF XY: 0.929

Gnomad AFR exome AF: 0.985

Gnomad AMR exome AF: 0.963

Gnomad ASJ exome AF: 0.906

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.925

Gnomad NFE exome AF: 0.903

Gnomad OTH exome AF: 0.921

GnomAD4 exome AF: 0.916 AC: 1338519 AN: 1461776 Hom.: 613481 Cov.: 53 AF XY: 0.915 AC XY: 665735 AN XY: 727188

African (AFR) AF: 0.989 AC: 33107 AN: 33476

American (AMR) AF: 0.964 AC: 43091 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.904 AC: 23633 AN: 26134

East Asian (EAS) AF: 1.00 AC: 39692 AN: 39700

South Asian (SAS) AF: 0.943 AC: 81309 AN: 86254

European-Finnish (FIN) AF: 0.922 AC: 49240 AN: 53420

Middle Eastern (MID) AF: 0.902 AC: 5200 AN: 5766

European-Non Finnish (NFE) AF: 0.906 AC: 1007516 AN: 1111912

Other (OTH) AF: 0.923 AC: 55731 AN: 60392

GnomAD4 genome AF: 0.936 AC: 142434 AN: 152254 Hom.: 66715 Cov.: 32 AF XY: 0.936 AC XY: 69673 AN XY: 74438

African (AFR) AF: 0.984 AC: 40890 AN: 41548

American (AMR) AF: 0.940 AC: 14370 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.917 AC: 3183 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5176 AN: 5180

South Asian (SAS) AF: 0.951 AC: 4586 AN: 4824

European-Finnish (FIN) AF: 0.923 AC: 9783 AN: 10602

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.902 AC: 61318 AN: 68014

Other (OTH) AF: 0.948 AC: 2007 AN: 2116

Alfa AF: 0.914 Hom.: 237573

Bravo AF: 0.941

TwinsUK AF: 0.909 AC: 3372

ALSPAC AF: 0.914 AC: 3521

ESP6500AA AF: 0.980 AC: 4317

ESP6500EA AF: 0.905 AC: 7781

ExAC AF: 0.932 AC: 113112

Asia WGS AF: 0.982 AC: 3417 AN: 3478

EpiCase AF: 0.899

EpiControl AF: 0.900

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Congenital anomalies of kidney and urinary tract 1 (1)
-	-	1	Hereditary spastic paraplegia 23 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.045
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	19
DANN	Benign	0.55
DEOGEN2	Benign	0.00077	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.40	T
MetaRNN	Benign	9.1e-7	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.4	N
PhyloP100		4.3
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	2.2	N
REVEL	Benign	0.21
Sift	Benign	0.57	T
Sift4G	Benign	0.18	T
Polyphen		0.0	B
Vest4		0.26
MPC		0.64
ClinPred		0.0059	T
GERP RS		5.3
Varity_R		0.19
gMVP		0.72
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3851294; hg19: chr1-205130413; COSMIC: COSV104675544;