1-205161285-A-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015375.3(DSTYK):​c.1921T>G​(p.Cys641Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign 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. C641R) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DSTYK NM_015375.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.27
• Publications: 54 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• hereditary spastic paraplegia 23

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: G2P, Orphanet
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17635307).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSTYK	NM_015375.3	MANE Select	c.1921T>G	p.Cys641Gly	missense	Exon 7 of 13	NP_056190.1
	DSTYK	NM_199462.3		c.1921T>G	p.Cys641Gly	missense	Exon 7 of 12	NP_955749.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSTYK	ENST00000367162.8	TSL:1 MANE Select	c.1921T>G	p.Cys641Gly	missense	Exon 7 of 13	ENSP00000356130.3
	DSTYK	ENST00000367161.7	TSL:1	c.1921T>G	p.Cys641Gly	missense	Exon 7 of 12	ENSP00000356129.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 53

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.0023	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.0	N
PhyloP100		4.3
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.18
Sift	Benign	0.060	T
Sift4G	Benign	0.14	T
Polyphen		0.0	B
Vest4		0.30
MutPred		0.66		Gain of disorder (P = 0.0067)
MVP		0.41
MPC		0.45
ClinPred		0.54	D
GERP RS		5.3
Varity_R		0.094
gMVP		0.77
Mutation Taster		=96/4	polymorphism

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;