11-33303830-A-T

Variant names:

• chr11-33303830-A-T
• rs16924133
• NM_005734.5:c.1097+16319A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005734.5(HIPK3):​c.1097+16319A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0981 in 152,258 control chromosomes in the GnomAD database, including 1,666 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 0.098 (1666 hom., cov: 32)
• Consequence: HIPK3 NM_005734.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.02
• Publications: 9 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=-0.47).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HIPK3	NM_005734.5	c.1097+16319A>T		intron_variant	Intron 2 of 16	ENST00000303296.9	NP_005725.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HIPK3	ENST00000303296.9	c.1097+16319A>T		intron_variant	Intron 2 of 16	5	NM_005734.5	ENSP00000304226.4
HIPK3	ENST00000379016.7	c.1097+16319A>T		intron_variant	Intron 2 of 15	1		ENSP00000368301.3
HIPK3	ENST00000525975.5	c.1097+16319A>T		intron_variant	Intron 2 of 15	1		ENSP00000431710.1
HIPK3	ENST00000456517.2	c.1097+16319A>T		intron_variant	Intron 2 of 15	2		ENSP00000398241.1

Frequencies

GnomAD3 genomes AF: 0.0981 AC: 14925 AN: 152140 Hom.: 1667 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0493

Gnomad ASJ AF: 0.0585

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0172

Gnomad FIN AF: 0.0198

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0291

Gnomad OTH AF: 0.0899

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

GnomAD4 genome AF: 0.0981 AC: 14938 AN: 152258 Hom.: 1666 Cov.: 32 AF XY: 0.0947 AC XY: 7054 AN XY: 74462

African (AFR) AF: 0.277 AC: 11503 AN: 41502

American (AMR) AF: 0.0491 AC: 751 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0585 AC: 203 AN: 3470

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5192

South Asian (SAS) AF: 0.0166 AC: 80 AN: 4830

European-Finnish (FIN) AF: 0.0198 AC: 210 AN: 10616

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0291 AC: 1981 AN: 68032

Other (OTH) AF: 0.0894 AC: 189 AN: 2114

Alfa AF: 0.0713 Hom.: 121

Bravo AF: 0.109

Asia WGS AF: 0.0300 AC: 104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	20
DANN	Benign	0.62
PhyloP100		2.0
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: rs16924133; hg19: chr11-33325376;