13-33016472-G-GGCC
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_004795.4(KL):c.43_45dup(p.Pro15dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 1,062,538 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000027 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000034 ( 0 hom. )
Consequence
KL
NM_004795.4 inframe_insertion
NM_004795.4 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.323
Genes affected
KL (HGNC:6344): (klotho) This gene encodes a type-I membrane protein that is related to beta-glucosidases. Reduced production of this protein has been observed in patients with chronic renal failure (CRF), and this may be one of the factors underlying the degenerative processes (e.g., arteriosclerosis, osteoporosis, and skin atrophy) seen in CRF. Also, mutations within this protein have been associated with ageing and bone loss. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_004795.4. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KL | NM_004795.4 | c.43_45dup | p.Pro15dup | inframe_insertion | 1/5 | ENST00000380099.4 | NP_004786.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KL | ENST00000380099.4 | c.43_45dup | p.Pro15dup | inframe_insertion | 1/5 | 1 | NM_004795.4 | ENSP00000369442 | P1 | |
KL | ENST00000487852.1 | n.51_53dup | non_coding_transcript_exon_variant | 1/5 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000274 AC: 4AN: 145980Hom.: 0 Cov.: 31
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GnomAD4 exome AF: 0.0000338 AC: 31AN: 916558Hom.: 0 Cov.: 27 AF XY: 0.0000303 AC XY: 13AN XY: 429192
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GnomAD4 genome AF: 0.0000274 AC: 4AN: 145980Hom.: 0 Cov.: 31 AF XY: 0.0000282 AC XY: 2AN XY: 70946
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 27, 2022 | This variant, c.43_45dup, results in the insertion of 1 amino acid(s) of the KL protein (p.Pro15dup), but otherwise preserves the integrity of the reading frame. 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 variant has not been reported in the literature in individuals affected with KL-related conditions. 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. - |
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at