chr1-113952814-G-A

Variant names:

• chr1-113952814-G-A
• ENST00000340480.8:c.3G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PVS1_Supporting PM2

The NM_198269.3(HIPK1):​c.3G>A​(p.Met1?) variant causes a start lost 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_198269.3 start_lost
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.97
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PVS1: Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 93 codons. Genomic position: 113955641. Lost 0.110 part of the original CDS.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198269.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIPK1	NM_198268.3	MANE Select	c.1125G>A	p.Met375Ile	missense	Exon 3 of 16	NP_938009.1	Q86Z02-1
	HIPK1	NM_198269.3		c.3G>A	p.Met1?	start_lost	Exon 2 of 15	NP_938010.1	Q86Z02-3
	HIPK1	NM_001369806.1		c.1125G>A	p.Met375Ile	missense	Exon 3 of 16	NP_001356735.1	Q86Z02-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIPK1	ENST00000340480.8	TSL:1	c.3G>A	p.Met1?	start_lost	Exon 2 of 15	ENSP00000340956.4	Q86Z02-3
	HIPK1	ENST00000426820.7	TSL:2 MANE Select	c.1125G>A	p.Met375Ile	missense	Exon 3 of 16	ENSP00000407442.3	Q86Z02-1
	HIPK1	ENST00000369558.5	TSL:1	c.1125G>A	p.Met375Ile	missense	Exon 3 of 16	ENSP00000358571.1	Q86Z02-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1378740 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 685636

African (AFR) AF: 0.00 AC: 0 AN: 29934

American (AMR) AF: 0.00 AC: 0 AN: 37420

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23726

East Asian (EAS) AF: 0.00 AC: 0 AN: 35574

South Asian (SAS) AF: 0.00 AC: 0 AN: 73338

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50522

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5412

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1067040

Other (OTH) AF: 0.00 AC: 0 AN: 55774

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.57
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	0.40	N
PhyloP100		10
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.49
Sift	Benign	0.078	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.70	P
Vest4		0.86
MutPred		0.60		Gain of catalytic residue at S377 (P = 0.3435)
MVP		0.98
MPC		1.8
ClinPred		0.93	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.53
gMVP		0.83
Mutation Taster		=9/191	disease causing

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

Other links and lift over

hg19: chr1-114495436;