rs5763911

Positions:

• chr22-20443002-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000328879.9(KLHL22):​c.1540-564A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0388 in 152,282 control chromosomes in the GnomAD database, including 167 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 0.039 (167 hom., cov: 33)
• Consequence: KLHL22 ENST00000328879.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42

Genes affected

KLHL22 (HGNC:25888): (kelch like family member 22) Enables 14-3-3 protein binding activity. Involved in several processes, including cellular protein metabolic process; cellular response to leucine; and mitotic spindle assembly checkpoint signaling. Located in several cellular components, including cytosol; intercellular bridge; and microtubule cytoskeleton. Part of Cul3-RING ubiquitin ligase complex. Colocalizes with lysosome and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

LOC107985588 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0952 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL22	NM_032775.4	c.1540-564A>G		intron_variant		ENST00000328879.9	NP_116164.2
LOC107985588	XR_001755623.2	n.695T>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL22	ENST00000328879.9	c.1540-564A>G		intron_variant		1	NM_032775.4	ENSP00000331682	P1

Frequencies

GnomAD3 genomes AF: 0.0387 AC: 5896 AN: 152164 Hom.: 168 Cov.: 33

Gnomad AFR AF: 0.00994

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0637

Gnomad ASJ AF: 0.0674

Gnomad EAS AF: 0.0867

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0247

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0431

Gnomad OTH AF: 0.0485

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

GnomAD4 genome AF: 0.0388 AC: 5903 AN: 152282 Hom.: 167 Cov.: 33 AF XY: 0.0404 AC XY: 3005 AN XY: 74450

Gnomad4 AFR AF: 0.00991

Gnomad4 AMR AF: 0.0639

Gnomad4 ASJ AF: 0.0674

Gnomad4 EAS AF: 0.0867

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.0247

Gnomad4 NFE AF: 0.0431

Gnomad4 OTH AF: 0.0480

Alfa AF: 0.0420 Hom.: 21

Bravo AF: 0.0414

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	12
DANN	Benign	0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs5763911; hg19: chr22-20797289;