15-39589946-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PP2PP3_Moderate
The NM_003246.4(THBS1):c.2068G>A(p.Gly690Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_003246.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
THBS1 | NM_003246.4 | c.2068G>A | p.Gly690Arg | missense_variant | 13/22 | ENST00000260356.6 | |
THBS1 | XM_047432980.1 | c.2068G>A | p.Gly690Arg | missense_variant | 13/22 | ||
THBS1 | XM_011521971.3 | c.1894G>A | p.Gly632Arg | missense_variant | 12/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
THBS1 | ENST00000260356.6 | c.2068G>A | p.Gly690Arg | missense_variant | 13/22 | 1 | NM_003246.4 | P1 | |
FSIP1 | ENST00000642527.1 | c.*215-1372C>T | intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000798 AC: 2AN: 250580Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135446
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461670Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727106
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74352
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 17, 2023 | The c.2068G>A (p.G690R) alteration is located in exon 13 (coding exon 12) of the THBS1 gene. This alteration results from a G to A substitution at nucleotide position 2068, causing the glycine (G) at amino acid position 690 to be replaced by an arginine (R). 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