13-69707668-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_020866.3(KLHL1):c.2144A>G(p.Asn715Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000219 in 1,460,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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. N715K) has been classified as Uncertain significance.
Frequency
Consequence
NM_020866.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KLHL1 | NM_020866.3 | c.2144A>G | p.Asn715Ser | missense_variant | 10/11 | ENST00000377844.9 | |
KLHL1 | NM_001286725.2 | c.1961A>G | p.Asn654Ser | missense_variant | 9/10 | ||
KLHL1 | XM_017020678.3 | c.1625A>G | p.Asn542Ser | missense_variant | 10/11 | ||
KLHL1 | XM_017020679.2 | c.1475A>G | p.Asn492Ser | missense_variant | 10/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KLHL1 | ENST00000377844.9 | c.2144A>G | p.Asn715Ser | missense_variant | 10/11 | 1 | NM_020866.3 | P1 | |
KLHL1 | ENST00000545028.2 | c.1961A>G | p.Asn654Ser | missense_variant | 9/10 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 250856Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135564
GnomAD4 exome AF: 0.0000219 AC: 32AN: 1460566Hom.: 0 Cov.: 31 AF XY: 0.0000234 AC XY: 17AN XY: 726580
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 24, 2022 | The c.2144A>G (p.N715S) alteration is located in exon 10 (coding exon 10) of the KLHL1 gene. This alteration results from a A to G substitution at nucleotide position 2144, causing the asparagine (N) at amino acid position 715 to be replaced by a serine (S). 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