1-205147915-TAAA-TAA

Variant names:

• chr1-205147915-TA-T
• rs35284794
• NM_015375.3:c.2603-171delT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_015375.3(DSTYK):​c.2603-171delT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.00019 (0 hom., cov: 0)
• Consequence: DSTYK NM_015375.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.28
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

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.2603-171delT		intron	N/A	NP_056190.1	Q6XUX3-1
	DSTYK	NM_199462.3		c.2468-171delT		intron	N/A	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.2603-171delT		intron	N/A	ENSP00000356130.3	Q6XUX3-1
	DSTYK	ENST00000367161.7	TSL:1	c.2468-171delT		intron	N/A	ENSP00000356129.3	Q6XUX3-2
	DSTYK	ENST00000893236.1		c.2576-171delT		intron	N/A	ENSP00000563295.1

Frequencies

GnomAD3 genomes AF: 0.000187 AC: 27 AN: 144402 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000343

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000200

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000548

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000751

Gnomad OTH AF: 0.000504

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.000187 AC: 27 AN: 144482 Hom.: 0 Cov.: 0 AF XY: 0.000157 AC XY: 11 AN XY: 70154

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000342 AC: 13 AN: 37996

American (AMR) AF: 0.000136 AC: 2 AN: 14654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3396

East Asian (EAS) AF: 0.000200 AC: 1 AN: 4988

South Asian (SAS) AF: 0.00 AC: 0 AN: 4598

European-Finnish (FIN) AF: 0.000548 AC: 5 AN: 9124

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000751 AC: 5 AN: 66536

Other (OTH) AF: 0.000499 AC: 1 AN: 2006

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000000920845), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 743

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-3.3

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: rs35284794; hg19: chr1-205117043;