chr1-205147507-A-T

Variant names:

• chr1-205147507-A-T
• rs11367
• NM_015375.3:c.*51T>A

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.*51T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 1,562,506 control chromosomes in the GnomAD database, including 40,071 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3504 hom., cov: 31)
  • Exomes 𝑓: 0.21 (36567 hom.)
• Consequence: DSTYK NM_015375.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.94
• Publications: 13 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 (BayesDel_noAF=-0.49).
• BP6: Variant 1-205147507-A-T is Benign according to our data. Variant chr1-205147507-A-T is described in ClinVar as Benign. ClinVar VariationId is 1244575.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.499 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.*51T>A		3_prime_UTR	Exon 13 of 13	NP_056190.1	Q6XUX3-1
	DSTYK	NM_199462.3		c.*51T>A		3_prime_UTR	Exon 12 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.*51T>A		3_prime_UTR	Exon 13 of 13	ENSP00000356130.3	Q6XUX3-1
	DSTYK	ENST00000367161.7	TSL:1	c.*51T>A		3_prime_UTR	Exon 12 of 12	ENSP00000356129.3	Q6XUX3-2
	DSTYK	ENST00000893236.1		c.*51T>A		3_prime_UTR	Exon 13 of 13	ENSP00000563295.1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28617 AN: 152048 Hom.: 3503 Cov.: 31

Gnomad AFR AF: 0.0746

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.195

GnomAD2 exomes AF: 0.252 AC: 59011 AN: 234498 AF XY: 0.255

Gnomad AFR exome AF: 0.0696

Gnomad AMR exome AF: 0.346

Gnomad ASJ exome AF: 0.189

Gnomad EAS exome AF: 0.509

Gnomad FIN exome AF: 0.179

Gnomad NFE exome AF: 0.199

Gnomad OTH exome AF: 0.243

GnomAD4 exome AF: 0.215 AC: 303076 AN: 1410338 Hom.: 36567 Cov.: 27 AF XY: 0.220 AC XY: 152818 AN XY: 695780

African (AFR) AF: 0.0676 AC: 2161 AN: 31970

American (AMR) AF: 0.335 AC: 13593 AN: 40606

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 4542 AN: 24178

East Asian (EAS) AF: 0.499 AC: 19368 AN: 38806

South Asian (SAS) AF: 0.360 AC: 29670 AN: 82390

European-Finnish (FIN) AF: 0.182 AC: 9503 AN: 52302

Middle Eastern (MID) AF: 0.292 AC: 1620 AN: 5554

European-Non Finnish (NFE) AF: 0.194 AC: 209170 AN: 1076524

Other (OTH) AF: 0.232 AC: 13449 AN: 58008

GnomAD4 genome AF: 0.188 AC: 28625 AN: 152168 Hom.: 3504 Cov.: 31 AF XY: 0.193 AC XY: 14391 AN XY: 74394

African (AFR) AF: 0.0745 AC: 3096 AN: 41546

American (AMR) AF: 0.270 AC: 4128 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 687 AN: 3472

East Asian (EAS) AF: 0.515 AC: 2657 AN: 5158

South Asian (SAS) AF: 0.370 AC: 1780 AN: 4814

European-Finnish (FIN) AF: 0.170 AC: 1799 AN: 10600

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13671 AN: 67980

Other (OTH) AF: 0.201 AC: 425 AN: 2114

Alfa AF: 0.137 Hom.: 375

Bravo AF: 0.189

Asia WGS AF: 0.443 AC: 1537 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Benign	0.87
PhyloP100		2.9
Mutation Taster		=100/0	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: rs11367; hg19: chr1-205116635; COSMIC: COSV65685860;