10-70708643-C-T
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_080722.4(ADAMTS14):c.735C>T(p.Gly245=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00148 in 1,612,772 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0075 ( 18 hom., cov: 31)
Exomes 𝑓: 0.00086 ( 16 hom. )
Consequence
ADAMTS14
NM_080722.4 synonymous
NM_080722.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.35
Genes affected
ADAMTS14 (HGNC:14899): (ADAM metallopeptidase with thrombospondin type 1 motif 14) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) protein family. Members of the family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme cleaves amino-terminal propeptides from type I procollagen, a necessary step in the formation of collagen fibers. Mutations in this gene may be associated with osteoarthritis in human patients. [provided by RefSeq, May 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
?
Variant 10-70708643-C-T is Benign according to our data. Variant chr10-70708643-C-T is described in ClinVar as [Benign]. Clinvar id is 788428.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-3.35 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0075 (1141/152150) while in subpopulation AFR AF= 0.026 (1079/41496). AF 95% confidence interval is 0.0247. There are 18 homozygotes in gnomad4. There are 564 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 18 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADAMTS14 | NM_080722.4 | c.735C>T | p.Gly245= | synonymous_variant | 4/22 | ENST00000373207.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADAMTS14 | ENST00000373207.2 | c.735C>T | p.Gly245= | synonymous_variant | 4/22 | 1 | NM_080722.4 | P4 | |
ADAMTS14 | ENST00000373208.5 | c.735C>T | p.Gly245= | synonymous_variant | 4/22 | 2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00748 AC: 1137AN: 152032Hom.: 18 Cov.: 31
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GnomAD3 exomes AF: 0.00194 AC: 486AN: 250858Hom.: 8 AF XY: 0.00144 AC XY: 196AN XY: 135688
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GnomAD4 exome AF: 0.000858 AC: 1253AN: 1460622Hom.: 16 Cov.: 32 AF XY: 0.000746 AC XY: 542AN XY: 726454
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GnomAD4 genome ? AF: 0.00750 AC: 1141AN: 152150Hom.: 18 Cov.: 31 AF XY: 0.00758 AC XY: 564AN XY: 74386
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 25, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
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Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at