chr22-20464958-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP3
The NM_032775.4(KLHL22):c.1012C>T(p.Arg338Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000622 in 1,606,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R338H) has been classified as Uncertain significance.
Frequency
Consequence
NM_032775.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KLHL22 | NM_032775.4 | c.1012C>T | p.Arg338Cys | missense_variant | 4/7 | ENST00000328879.9 | |
LOC124905085 | XR_007068014.1 | n.132+3852G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KLHL22 | ENST00000328879.9 | c.1012C>T | p.Arg338Cys | missense_variant | 4/7 | 1 | NM_032775.4 | P1 | |
KLHL22 | ENST00000479601.5 | n.1078C>T | non_coding_transcript_exon_variant | 4/5 | 5 | ||||
KLHL22 | ENST00000487090.1 | n.153+376C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152188Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000123 AC: 3AN: 244012Hom.: 0 AF XY: 0.00000759 AC XY: 1AN XY: 131760
GnomAD4 exome AF: 0.00000619 AC: 9AN: 1454688Hom.: 0 Cov.: 32 AF XY: 0.00000415 AC XY: 3AN XY: 723370
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152188Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74346
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 31, 2023 | The c.1012C>T (p.R338C) alteration is located in exon 4 (coding exon 3) of the KLHL22 gene. This alteration results from a C to T substitution at nucleotide position 1012, causing the arginine (R) at amino acid position 338 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at