rs5763911

Variant names:

• chr22-20443002-T-C
• rs5763911
• NM_032775.4:c.1540-564A>G

Variant summary

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

The NM_032775.4(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 NM_032775.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• Publications: 6 publications found

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]

ENSG00000277971 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KLHL22	NM_032775.4	c.1540-564A>G		intron_variant	Intron 6 of 6	ENST00000328879.9	NP_116164.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL22	ENST00000328879.9	c.1540-564A>G		intron_variant	Intron 6 of 6	1	NM_032775.4	ENSP00000331682.4
ENSG00000277971	ENST00000429594.1	n.177+3441A>G		intron_variant	Intron 1 of 4	5		ENSP00000392268.1

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

African (AFR) AF: 0.00991 AC: 412 AN: 41562

American (AMR) AF: 0.0639 AC: 977 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0674 AC: 234 AN: 3472

East Asian (EAS) AF: 0.0867 AC: 450 AN: 5190

South Asian (SAS) AF: 0.103 AC: 495 AN: 4822

European-Finnish (FIN) AF: 0.0247 AC: 262 AN: 10614

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0431 AC: 2929 AN: 68022

Other (OTH) AF: 0.0480 AC: 101 AN: 2106

Alfa AF: 0.0386 Hom.: 92

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
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5763911; hg19: chr22-20797289;