rs266489

Positions:

• chr11-33331063-A-G
• chr11-33331063-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_005734.5(HIPK3):​c.1221+2430A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0141 in 151,834 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.014 (56 hom., cov: 32)
• Consequence: HIPK3 NM_005734.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

Genes affected

HIPK3 (HGNC:4915): (homeodomain interacting protein kinase 3) Enables protein serine/threonine kinase activity. Involved in mRNA transcription; negative regulation of apoptotic process; and protein phosphorylation. Located in cytosol; nuclear body; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0141 (2146/151834) while in subpopulation AFR AF= 0.0487 (2017/41386). AF 95% confidence interval is 0.047. There are 56 homozygotes in gnomad4. There are 1042 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2146 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HIPK3	NM_005734.5	c.1221+2430A>G		intron_variant		ENST00000303296.9	NP_005725.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HIPK3	ENST00000303296.9	c.1221+2430A>G		intron_variant		5	NM_005734.5	ENSP00000304226	A1

Frequencies

GnomAD3 genomes AF: 0.0141 AC: 2134 AN: 151716 Hom.: 56 Cov.: 32

Gnomad AFR AF: 0.0486

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00591

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0101

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0141 AC: 2146 AN: 151834 Hom.: 56 Cov.: 32 AF XY: 0.0140 AC XY: 1042 AN XY: 74240

Gnomad4 AFR AF: 0.0487

Gnomad4 AMR AF: 0.00590

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.000625

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.00996

Alfa AF: 0.00814 Hom.: 4

Bravo AF: 0.0159

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.26

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

Other links and lift over

dbSNP: rs266489; hg19: chr11-33352609;