3-49173094-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4BS2_Supporting
The NM_173546.3(KLHDC8B):c.325C>T(p.Arg109Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000177 in 1,584,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. R109H) has been classified as Uncertain significance.
Frequency
Consequence
NM_173546.3 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 |
---|---|---|---|---|---|---|---|
KLHDC8B | NM_173546.3 | c.325C>T | p.Arg109Cys | missense_variant | 2/6 | ENST00000332780.4 | |
KLHDC8B | XM_006713015.4 | c.325C>T | p.Arg109Cys | missense_variant | 2/6 | ||
KLHDC8B | XM_006713016.4 | c.325C>T | p.Arg109Cys | missense_variant | 2/6 | ||
KLHDC8B | XM_005264938.4 | c.325C>T | p.Arg109Cys | missense_variant | 2/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KLHDC8B | ENST00000332780.4 | c.325C>T | p.Arg109Cys | missense_variant | 2/6 | 1 | NM_173546.3 | P1 | |
KLHDC8B | ENST00000476495.2 | n.382C>T | non_coding_transcript_exon_variant | 1/3 | 2 | ||||
KLHDC8B | ENST00000459846.6 | n.230+293C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152154Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000204 AC: 4AN: 195910Hom.: 0 AF XY: 0.0000284 AC XY: 3AN XY: 105504
GnomAD4 exome AF: 0.0000175 AC: 25AN: 1432252Hom.: 0 Cov.: 31 AF XY: 0.0000155 AC XY: 11AN XY: 710134
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152154Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74318
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 07, 2023 | An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant  is likely to be tolerated. 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. This variant has not been reported in the literature in individuals affected with KLHDC8B-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 109 of the KLHDC8B protein (p.Arg109Cys). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at