8-102650265-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_005655.4(KLF10):c.1310G>A(p.Arg437Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R437W) has been classified as Uncertain significance.
Frequency
Consequence
NM_005655.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KLF10 | NM_005655.4 | c.1310G>A | p.Arg437Gln | missense_variant | Exon 4 of 4 | ENST00000285407.11 | NP_005646.1 | |
KLF10 | NM_001032282.4 | c.1277G>A | p.Arg426Gln | missense_variant | Exon 4 of 4 | NP_001027453.1 | ||
KLF10 | NR_103759.2 | n.635G>A | non_coding_transcript_exon_variant | Exon 3 of 3 | ||||
KLF10 | NR_103760.2 | n.758G>A | non_coding_transcript_exon_variant | Exon 4 of 4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KLF10 | ENST00000285407.11 | c.1310G>A | p.Arg437Gln | missense_variant | Exon 4 of 4 | 1 | NM_005655.4 | ENSP00000285407.6 | ||
KLF10 | ENST00000395884.3 | c.1277G>A | p.Arg426Gln | missense_variant | Exon 4 of 4 | 1 | ENSP00000379222.3 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251452Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135910
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461894Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727248
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces arginine with glutamine at codon 437 of the KLF10 protein (p.Arg437Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs780387658, ExAC 0.001%). This variant has not been reported in the literature in individuals affected with KLF10-related conditions. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at