chr1-6593396-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_014851.4(KLHL21):c.1763G>A(p.Arg588Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000592 in 1,604,710 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 (★).
Frequency
Consequence
NM_014851.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KLHL21 | NM_014851.4 | c.1763G>A | p.Arg588Gln | missense_variant | 4/4 | ENST00000377658.8 | |
KLHL21 | NM_001324309.2 | c.*712G>A | 3_prime_UTR_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KLHL21 | ENST00000377658.8 | c.1763G>A | p.Arg588Gln | missense_variant | 4/4 | 1 | NM_014851.4 | P1 | |
KLHL21 | ENST00000496707.5 | c.662G>A | p.Arg221Gln | missense_variant | 4/4 | 1 | |||
KLHL21 | ENST00000377663.3 | c.*1969G>A | 3_prime_UTR_variant | 3/3 | 1 | ||||
KLHL21 | ENST00000467612.5 | c.662G>A | p.Arg221Gln | missense_variant | 4/4 | 3 |
Frequencies
GnomAD3 genomes AF: 0.000335 AC: 51AN: 152214Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000740 AC: 18AN: 243180Hom.: 0 AF XY: 0.0000452 AC XY: 6AN XY: 132722
GnomAD4 exome AF: 0.0000303 AC: 44AN: 1452378Hom.: 0 Cov.: 31 AF XY: 0.0000249 AC XY: 18AN XY: 721832
GnomAD4 genome AF: 0.000335 AC: 51AN: 152332Hom.: 0 Cov.: 33 AF XY: 0.000295 AC XY: 22AN XY: 74484
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 21, 2024 | The c.1763G>A (p.R588Q) alteration is located in exon 4 (coding exon 4) of the KLHL21 gene. This alteration results from a G to A substitution at nucleotide position 1763, causing the arginine (R) at amino acid position 588 to be replaced by a glutamine (Q). 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