chr9-21333136-T-C
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_018847.4(KLHL9):āc.1724A>Gā(p.His575Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,614,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_018847.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KLHL9 | NM_018847.4 | c.1724A>G | p.His575Arg | missense_variant | 1/1 | ENST00000359039.5 | |
LOC107987053 | XR_001746634.2 | n.472-3485T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KLHL9 | ENST00000359039.5 | c.1724A>G | p.His575Arg | missense_variant | 1/1 | NM_018847.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152230Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251400Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135868
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461874Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3AN XY: 727234
GnomAD4 genome AF: 0.00000656 AC: 1AN: 152348Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74510
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 25, 2021 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). This variant has not been reported in the literature in individuals affected with KLHL9-related conditions. This variant is present in population databases (rs145825708, ExAC 0.01%). This sequence change replaces histidine with arginine at codon 575 of the KLHL9 protein (p.His575Arg). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and arginine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at