rs772766622

Variant names:

• chr1-113940424-C-G
• NM_198268.3:c.41C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-113940424-C-G
• chr1-113940424-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_198268.3(HIPK1):​c.41C>G​(p.Ser14Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S14L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: HIPK1 NM_198268.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.19

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38859767).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HIPK1	NM_198268.3	c.41C>G	p.Ser14Trp	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.41C>G	p.Ser14Trp	missense_variant	Exon 2 of 16	2	NM_198268.3	ENSP00000407442.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460914 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726682

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.41	T;.;T;T;.;T;.;.
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Pathogenic	0.99	.;D;D;D;D;.;D;D
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.39	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.1	M;M;.;M;.;.;.;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-2.9	.;D;.;D;D;D;D;D
REVEL	Benign	0.23
Sift	Uncertain	0.0030	.;D;.;D;D;D;D;D
Sift4G	Uncertain	0.0050	D;D;D;D;D;D;D;D
Polyphen		1.0	D;D;.;D;.;.;.;.
Vest4		0.55
MutPred		0.39		Loss of disorder (P = 1e-04);Loss of disorder (P = 1e-04);Loss of disorder (P = 1e-04);Loss of disorder (P = 1e-04);Loss of disorder (P = 1e-04);Loss of disorder (P = 1e-04);Loss of disorder (P = 1e-04);Loss of disorder (P = 1e-04);
MVP		0.52
MPC		0.95
ClinPred		0.95	D
GERP RS		4.9
Varity_R		0.46
gMVP		0.40

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.

Other links and lift over

hg19: chr1-114483046;