1-113940923-T-G

Variant names:

• chr1-113940923-T-G
• rs1670606425
• NM_198268.3:c.540T>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_198268.3(HIPK1):​c.540T>G​(p.His180Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00063 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HIPK1 NM_198268.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.40

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HIPK1	NM_198268.3	c.540T>G	p.His180Gln	missense_variant	Exon 2 of 16	ENST00000426820.7	NP_938009.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HIPK1	ENST00000426820.7	c.540T>G	p.His180Gln	missense_variant	Exon 2 of 16	2	NM_198268.3	ENSP00000407442.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 11 AN: 151668 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000571

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000442

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000627 AC: 896 AN: 1429438 Hom.: 0 Cov.: 32 AF XY: 0.000567 AC XY: 404 AN XY: 712114

Gnomad4 AFR exome AF: 0.000488

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000193

Gnomad4 EAS exome AF: 0.000178

Gnomad4 SAS exome AF: 0.000257

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000753

Gnomad4 OTH exome AF: 0.000489

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000725 AC: 11 AN: 151788 Hom.: 0 Cov.: 32 AF XY: 0.0000674 AC XY: 5 AN XY: 74220

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000571

Gnomad4 NFE AF: 0.0000442

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 12, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.540T>G (p.H180Q) alteration is located in exon 2 (coding exon 1) of the HIPK1 gene. This alteration results from a T to G substitution at nucleotide position 540, causing the histidine (H) at amino acid position 180 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.092	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.61	D;.;T;D;.;T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Pathogenic	0.98	.;D;D;D;D;.
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.69	D;D;D;D;D;D
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.5	M;M;.;M;.;.
PrimateAI	Pathogenic	0.89	D
PROVEAN	Pathogenic	-7.5	.;D;.;D;D;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0010	.;D;.;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D
Polyphen		0.99	D;D;.;D;.;.
Vest4		0.81
MutPred		0.56		Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);
MVP		0.70
MPC		1.7
ClinPred		1.0	D
GERP RS		4.6
Varity_R		0.80
gMVP		0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs1670606425; hg19: chr1-114483545;