chr1-113956802-A-T

Variant names:

• chr1-113956802-A-T
• rs1438590067
• NM_198268.3:c.1583A>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_198268.3(HIPK1):​c.1583A>T​(p.His528Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. H528R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HIPK1 NM_198268.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.57
• Publications: 0 publications found

Genes affected

HIPK1 (HGNC:19006): (homeodomain interacting protein kinase 1) The protein encoded by this gene belongs to the Ser/Thr family of protein kinases and HIPK subfamily. It phosphorylates homeodomain transcription factors and may also function as a co-repressor for homeodomain transcription factors. Alternative splicing results in four transcript variants encoding four distinct isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.853

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198268.3. 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
	HIPK1	NM_198268.3	MANE Select	c.1583A>T	p.His528Leu	missense	Exon 6 of 16	NP_938009.1	Q86Z02-1
	HIPK1	NM_001369806.1		c.1583A>T	p.His528Leu	missense	Exon 6 of 16	NP_001356735.1	Q86Z02-1
	HIPK1	NM_001369807.1		c.1583A>T	p.His528Leu	missense	Exon 6 of 16	NP_001356736.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIPK1	ENST00000426820.7	TSL:2 MANE Select	c.1583A>T	p.His528Leu	missense	Exon 6 of 16	ENSP00000407442.3	Q86Z02-1
	HIPK1	ENST00000369558.5	TSL:1	c.1583A>T	p.His528Leu	missense	Exon 6 of 16	ENSP00000358571.1	Q86Z02-1
	HIPK1	ENST00000369559.8	TSL:1	c.1583A>T	p.His528Leu	missense	Exon 6 of 15	ENSP00000358572.4	Q86Z02-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	26
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.60	D
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.075	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Benign	-0.45	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		7.6
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-10	D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.90	P
Vest4		0.82
MutPred		0.46		Loss of catalytic residue at H528 (P = 0.0463)
MVP		0.85
MPC		0.75
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.79
gMVP		0.64
Mutation Taster		=60/40	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: rs1438590067; hg19: chr1-114499424;