1-113941434-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_198268.3(HIPK1):ā€‹c.1051A>Gā€‹(p.Thr351Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

HIPK1
NM_198268.3 missense

Scores

9
5
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.27
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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.872

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HIPK1NM_198268.3 linkuse as main transcriptc.1051A>G p.Thr351Ala missense_variant 2/16 ENST00000426820.7 NP_938009.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HIPK1ENST00000426820.7 linkuse as main transcriptc.1051A>G p.Thr351Ala missense_variant 2/162 NM_198268.3 ENSP00000407442 P1Q86Z02-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000797
AC:
2
AN:
250994
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135658
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000579
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461348
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
726898
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 23, 2021The c.1051A>G (p.T351A) alteration is located in exon 2 (coding exon 1) of the HIPK1 gene. This alteration results from a A to G substitution at nucleotide position 1051, causing the threonine (T) at amino acid position 351 to be replaced by an alanine (A). 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
0.89
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Pathogenic
0.21
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.35
T;.;T;T;.;T
Eigen
Uncertain
0.64
Eigen_PC
Pathogenic
0.68
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.95
.;D;D;D;D;.
M_CAP
Benign
0.034
D
MetaRNN
Pathogenic
0.87
D;D;D;D;D;D
MetaSVM
Benign
-0.58
T
MutationAssessor
Benign
1.0
L;L;.;L;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D
PrimateAI
Pathogenic
0.85
D
PROVEAN
Pathogenic
-4.7
.;D;.;D;D;D
REVEL
Pathogenic
0.72
Sift
Uncertain
0.0010
.;D;.;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D;D;D
Polyphen
0.98
D;P;.;D;.;.
Vest4
0.88
MutPred
0.67
Loss of methylation at K346 (P = 0.0815);Loss of methylation at K346 (P = 0.0815);Loss of methylation at K346 (P = 0.0815);Loss of methylation at K346 (P = 0.0815);Loss of methylation at K346 (P = 0.0815);Loss of methylation at K346 (P = 0.0815);
MVP
0.92
MPC
1.6
ClinPred
0.97
D
GERP RS
5.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.7
Varity_R
0.70
gMVP
0.71

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs1307734378; hg19: chr1-114484056; API