1-113958148-A-G

Variant names:

• chr1-113958148-A-G
• NM_198268.3:c.1838A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_198268.3(HIPK1):​c.1838A>G​(p.Gln613Arg) variant causes a missense change involving the alteration of a 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HIPK1 NM_198268.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.95

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 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
HIPK1	NM_198268.3	c.1838A>G	p.Gln613Arg	missense_variant	Exon 8 of 16	ENST00000426820.7	NP_938009.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HIPK1	ENST00000426820.7	c.1838A>G	p.Gln613Arg	missense_variant	Exon 8 of 16	2	NM_198268.3	ENSP00000407442.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 22, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1838A>G (p.Q613R) alteration is located in exon 8 (coding exon 7) of the HIPK1 gene. This alteration results from a A to G substitution at nucleotide position 1838, causing the glutamine (Q) at amino acid position 613 to be replaced by an arginine (R). 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	Benign	0.29
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.13
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;.;T;T;.;T;.;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	.;D;D;D;T;.;D;D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.70	D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.3	M;M;.;M;.;.;.;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.8	.;N;.;N;N;N;N;N
REVEL	Uncertain	0.36
Sift	Uncertain	0.0060	.;D;.;D;T;D;D;D
Sift4G	Benign	0.24	T;T;T;T;T;T;T;T
Polyphen		0.97	D;B;.;D;.;.;.;B
Vest4		0.79
MutPred		0.25		Gain of methylation at Q613 (P = 0.0312);Gain of methylation at Q613 (P = 0.0312);Gain of methylation at Q613 (P = 0.0312);Gain of methylation at Q613 (P = 0.0312);.;Gain of methylation at Q613 (P = 0.0312);.;.;
MVP		0.82
MPC		0.42
ClinPred		0.87	D
GERP RS		5.2
Varity_R		0.16
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-114500770;