1-113940883-G-C

Variant names:

• chr1-113940883-G-C
• rs759807796
• NM_198268.3:c.500G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_198268.3(HIPK1):​c.500G>C​(p.Ser167Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. S167N) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: HIPK1 NM_198268.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.05
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27127525).

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.500G>C	p.Ser167Thr	missense	Exon 2 of 16	NP_938009.1	Q86Z02-1
	HIPK1	NM_001369806.1		c.500G>C	p.Ser167Thr	missense	Exon 2 of 16	NP_001356735.1	Q86Z02-1
	HIPK1	NM_001369807.1		c.500G>C	p.Ser167Thr	missense	Exon 2 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.500G>C	p.Ser167Thr	missense	Exon 2 of 16	ENSP00000407442.3	Q86Z02-1
	HIPK1	ENST00000369558.5	TSL:1	c.500G>C	p.Ser167Thr	missense	Exon 2 of 16	ENSP00000358571.1	Q86Z02-1
	HIPK1	ENST00000369559.8	TSL:1	c.500G>C	p.Ser167Thr	missense	Exon 2 of 15	ENSP00000358572.4	Q86Z02-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152196 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152196 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74356

African (AFR) AF: 0.00 AC: 0 AN: 41426

American (AMR) AF: 0.0000655 AC: 1 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68050

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Uncertain	0.45	T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		8.0
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.11
Sift	Benign	0.053	T
Sift4G	Benign	0.14	T
Polyphen		0.98	D
Vest4		0.39
MutPred		0.23		Loss of catalytic residue at S167 (P = 0.0423)
MVP		0.60
MPC		0.99
ClinPred		0.76	D
GERP RS		5.8
Varity_R		0.27
gMVP		0.43
Mutation Taster		=65/35	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: rs759807796; hg19: chr1-114483505;