1-205187714-C-G

Variant names:

• chr1-205187714-C-G
• rs373780579
• NM_015375.3:c.358G>C

Variant summary

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

The NM_015375.3(DSTYK):​c.358G>C​(p.Asp120His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. D120N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DSTYK NM_015375.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.91
• 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: 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSTYK	NM_015375.3	c.358G>C	p.Asp120His	missense_variant	Exon 2 of 13	ENST00000367162.8	NP_056190.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSTYK	ENST00000367162.8	c.358G>C	p.Asp120His	missense_variant	Exon 2 of 13	1	NM_015375.3	ENSP00000356130.3
DSTYK	ENST00000367161.7	c.358G>C	p.Asp120His	missense_variant	Exon 2 of 12	1		ENSP00000356129.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000251 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.081	.;T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Uncertain	0.090	D
MetaRNN	Uncertain	0.42	T;T
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Benign	1.9	L;L
PhyloP100		2.9
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.7	D;N
REVEL	Uncertain	0.49
Sift	Uncertain	0.0070	D;D
Sift4G	Uncertain	0.028	D;D
Polyphen		0.99	D;D
Vest4		0.36
MutPred		0.45		Loss of ubiquitination at K124 (P = 0.1151);Loss of ubiquitination at K124 (P = 0.1151);
MVP		0.75
MPC		0.90
ClinPred		0.94	D
GERP RS		3.6
Varity_R		0.15
gMVP		0.59
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs373780579; hg19: chr1-205156842;