rs266489

Variant names:

• chr11-33331063-A-G
• rs266489
• NM_005734.5:c.1221+2430A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2146 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005734.5. 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
	HIPK3	NM_005734.5	MANE Select	c.1221+2430A>G		intron	N/A	NP_005725.3
	HIPK3	NM_001048200.3		c.1221+2430A>G		intron	N/A	NP_001041665.1
	HIPK3	NM_001278162.2		c.1221+2430A>G		intron	N/A	NP_001265091.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIPK3	ENST00000303296.9	TSL:5 MANE Select	c.1221+2430A>G		intron	N/A	ENSP00000304226.4
	HIPK3	ENST00000379016.7	TSL:1	c.1221+2430A>G		intron	N/A	ENSP00000368301.3
	HIPK3	ENST00000525975.5	TSL:1	c.1221+2430A>G		intron	N/A	ENSP00000431710.1

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

African (AFR) AF: 0.0487 AC: 2017 AN: 41386

American (AMR) AF: 0.00590 AC: 90 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5140

South Asian (SAS) AF: 0.000625 AC: 3 AN: 4802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10544

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 67932

Other (OTH) AF: 0.00996 AC: 21 AN: 2108

Alfa AF: 0.00943 Hom.: 5

Bravo AF: 0.0159

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.26
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs266489; hg19: chr11-33352609;