Variant 1-113952814-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_198268.3(HIPK1):c.1125G>A(p.Met375Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HIPK1
NM_198268.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.97

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]

HIPK1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.745

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HIPK1	NM_198268.3 linkuse as main transcript	c.1125G>A	p.Met375Ile	missense_variant	3/16	ENST00000426820.7	NP_938009.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HIPK1	ENST00000426820.7 linkuse as main transcript	c.1125G>A	p.Met375Ile	missense_variant	3/16	2	NM_198268.3	ENSP00000407442	P1	Q86Z02-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1378740

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

685636

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 submitter

clinical testing

Ambry Genetics

Apr 07, 2022

The c.1125G>A (p.M375I) alteration is located in exon 3 (coding exon 2) of the HIPK1 gene. This alteration results from a G to A substitution at nucleotide position 1125, causing the methionine (M) at amino acid position 375 to be replaced by an isoleucine (I). 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

0.99

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.22

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

T;.;T;T;.;T;.

Eigen

Uncertain

0.57

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

.;D;D;D;D;.;D

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.73

D;D;D;D;D;D;D

MetaSVM

Benign

-0.64

MutationAssessor

Benign

0.40

N;N;.;N;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-2.2

N;D;.;D;D;D;D

REVEL

Uncertain

0.49

Sift

Benign

0.078

T;D;.;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;D

Polyphen

0.70

P;P;.;P;.;.;.

Vest4

0.86

MutPred

0.60

Gain of catalytic residue at S377 (P = 0.3435);Gain of catalytic residue at S377 (P = 0.3435);Gain of catalytic residue at S377 (P = 0.3435);Gain of catalytic residue at S377 (P = 0.3435);Gain of catalytic residue at S377 (P = 0.3435);Gain of catalytic residue at S377 (P = 0.3435);.;

MVP

0.98

MPC

1.8

ClinPred

0.93

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.53

gMVP

0.83

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over