1-113955618-A-T

Variant summary

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

The NM_198268.3(HIPK1):​c.1376A>T​(p.Tyr459Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,362 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

HIPK1
NM_198268.3 missense

Scores

6
7
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.32
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
HIPK1NM_198268.3 linkc.1376A>T p.Tyr459Phe missense_variant Exon 5 of 16 ENST00000426820.7 NP_938009.1 Q86Z02-1B4DZ33

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HIPK1ENST00000426820.7 linkc.1376A>T p.Tyr459Phe missense_variant Exon 5 of 16 2 NM_198268.3 ENSP00000407442.3 Q86Z02-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000798
AC:
2
AN:
250674
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135496
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.88e-7
AC:
1
AN:
1454362
Hom.:
0
Cov.:
26
AF XY:
0.00000138
AC XY:
1
AN XY:
723962
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.05e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000468
Hom.:
0
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 06, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1376A>T (p.Y459F) alteration is located in exon 5 (coding exon 4) of the HIPK1 gene. This alteration results from a A to T substitution at nucleotide position 1376, causing the tyrosine (Y) at amino acid position 459 to be replaced by a phenylalanine (F). 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
Uncertain
0.56
BayesDel_addAF
Uncertain
0.057
T
BayesDel_noAF
Benign
-0.14
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Benign
0.34
T;.;T;T;.;T;.;.
Eigen
Pathogenic
0.69
Eigen_PC
Pathogenic
0.68
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.99
.;D;D;D;D;.;D;D
M_CAP
Benign
0.0094
T
MetaRNN
Uncertain
0.54
D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.67
T
MutationAssessor
Benign
1.1
L;L;.;L;.;.;.;.
PrimateAI
Pathogenic
0.90
D
PROVEAN
Uncertain
-3.9
.;D;.;D;D;D;D;D
REVEL
Uncertain
0.43
Sift
Pathogenic
0.0
.;D;.;D;D;D;D;D
Sift4G
Uncertain
0.018
D;D;D;D;D;D;D;D
Polyphen
1.0
D;D;.;D;.;.;.;D
Vest4
0.71
MVP
0.70
MPC
1.7
ClinPred
0.99
D
GERP RS
5.1
Varity_R
0.75
gMVP
0.57

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs747808047; hg19: chr1-114498240; API