chr19-8580857-A-G
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_030957.4(ADAMTS10):c.*36T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000244 in 1,517,662 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 (★).
Frequency
Genomes: 𝑓 0.00020 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00025 ( 0 hom. )
Consequence
ADAMTS10
NM_030957.4 3_prime_UTR
NM_030957.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.688
Genes affected
ADAMTS10 (HGNC:13201): (ADAM metallopeptidase with thrombospondin type 1 motif 10) This gene belongs to the ADAMTS (a disintegrin and metalloproteinase domain with thrombospondin type-1 motifs) family of zinc-dependent proteases. ADAMTS proteases are complex secreted enzymes containing a prometalloprotease domain of the reprolysin type attached to an ancillary domain with a highly conserved structure that includes at least one thrombospondin type 1 repeat. They have been demonstrated to have important roles in connective tissue organization, coagulation, inflammation, arthritis, angiogenesis and cell migration. The product of this gene plays a major role in growth and in skin, lens, and heart development. It is also a candidate gene for autosomal recessive Weill-Marchesani syndrome. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000205 (31/151446) while in subpopulation NFE AF= 0.000369 (25/67824). AF 95% confidence interval is 0.000256. There are 0 homozygotes in gnomad4. There are 10 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| ADAMTS10 | NM_030957.4 | c.*36T>C | 3_prime_UTR_variant | 26/26 | ENST00000597188.6 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ADAMTS10 | ENST00000597188.6 | c.*36T>C | 3_prime_UTR_variant | 26/26 | 5 | NM_030957.4 | P1 | ||
| ADAMTS10 | ENST00000270328.8 | c.*36T>C | 3_prime_UTR_variant | 25/25 | 5 | P1 | |||
| ADAMTS10 | ENST00000595838.5 | c.*36T>C | 3_prime_UTR_variant | 13/13 | 2 | ||||
| ADAMTS10 | ENST00000593913.5 | c.*2225T>C | 3_prime_UTR_variant, NMD_transcript_variant | 22/22 | 5 |
Frequencies
GnomAD3 genomes 0.000205 AC: 31AN: 151336Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000918 AC: 16AN: 174278Hom.: 0 AF XY: 0.0000630 AC XY: 6AN XY: 95304
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GnomAD4 exome AF: 0.000248 AC: 339AN: 1366216Hom.: 0 Cov.: 26 AF XY: 0.000240 AC XY: 163AN XY: 678858
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GnomAD4 genome 0.000205 AC: 31AN: 151446Hom.: 0 Cov.: 31 AF XY: 0.000135 AC XY: 10AN XY: 73998
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Weill-Marchesani syndrome Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at