chr22-20465035-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_032775.4(KLHL22):āc.935C>Gā(p.Thr312Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000559 in 1,611,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_032775.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KLHL22 | NM_032775.4 | c.935C>G | p.Thr312Ser | missense_variant | 4/7 | ENST00000328879.9 | |
LOC124905085 | XR_007068014.1 | n.132+3929G>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KLHL22 | ENST00000328879.9 | c.935C>G | p.Thr312Ser | missense_variant | 4/7 | 1 | NM_032775.4 | P1 | |
KLHL22 | ENST00000479601.5 | n.1001C>G | non_coding_transcript_exon_variant | 4/5 | 5 | ||||
KLHL22 | ENST00000487090.1 | n.153+299C>G | intron_variant, non_coding_transcript_variant | 3 | |||||
KLHL22 | ENST00000451553.1 | downstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152220Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248920Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134538
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1459036Hom.: 0 Cov.: 32 AF XY: 0.00000276 AC XY: 2AN XY: 725548
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152220Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74370
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 16, 2024 | The c.935C>G (p.T312S) alteration is located in exon 4 (coding exon 3) of the KLHL22 gene. This alteration results from a C to G substitution at nucleotide position 935, causing the threonine (T) at amino acid position 312 to be replaced by a serine (S). 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