chr12-43425515-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_025003.5(ADAMTS20):c.4283C>T(p.Ser1428Leu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000528 in 1,505,714 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_025003.5 missense, splice_region
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 |
---|---|---|---|---|---|---|---|
ADAMTS20 | NM_025003.5 | c.4283C>T | p.Ser1428Leu | missense_variant, splice_region_variant | 28/39 | ENST00000389420.8 | |
ADAMTS20 | XM_011538754.3 | c.4286C>T | p.Ser1429Leu | missense_variant, splice_region_variant | 28/39 | ||
ADAMTS20 | XM_017019979.2 | c.3071C>T | p.Ser1024Leu | missense_variant, splice_region_variant | 21/32 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADAMTS20 | ENST00000389420.8 | c.4283C>T | p.Ser1428Leu | missense_variant, splice_region_variant | 28/39 | 1 | NM_025003.5 | P1 | |
ADAMTS20 | ENST00000553158.5 | c.4283C>T | p.Ser1428Leu | missense_variant, splice_region_variant | 28/29 | 5 | |||
ADAMTS20 | ENST00000549670.5 | c.1673C>T | p.Ser558Leu | missense_variant, splice_region_variant | 10/11 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000342 AC: 52AN: 152114Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000291 AC: 61AN: 209472Hom.: 0 AF XY: 0.000237 AC XY: 27AN XY: 113708
GnomAD4 exome AF: 0.000549 AC: 743AN: 1353482Hom.: 1 Cov.: 31 AF XY: 0.000512 AC XY: 341AN XY: 666222
GnomAD4 genome ? AF: 0.000342 AC: 52AN: 152232Hom.: 0 Cov.: 32 AF XY: 0.000322 AC XY: 24AN XY: 74442
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 01, 2021 | The c.4283C>T (p.S1428L) alteration is located in exon 28 (coding exon 28) of the ADAMTS20 gene. This alteration results from a C to T substitution at nucleotide position 4283, causing the serine (S) at amino acid position 1428 to be replaced by a leucine (L). 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