chr15-39593094-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_003246.4(THBS1):c.2862G>C(p.Glu954Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,446,882 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 (★).
Frequency
Consequence
NM_003246.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
THBS1 | NM_003246.4 | c.2862G>C | p.Glu954Asp | missense_variant | 18/22 | ENST00000260356.6 | |
THBS1 | XM_047432980.1 | c.2862G>C | p.Glu954Asp | missense_variant | 18/22 | ||
THBS1 | XM_011521971.3 | c.2688G>C | p.Glu896Asp | missense_variant | 17/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
THBS1 | ENST00000260356.6 | c.2862G>C | p.Glu954Asp | missense_variant | 18/22 | 1 | NM_003246.4 | P1 | |
THBS1 | ENST00000484734.1 | n.50G>C | non_coding_transcript_exon_variant | 1/4 | 5 | ||||
FSIP1 | ENST00000642527.1 | c.*214+961C>G | intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000127 AC: 3AN: 235706Hom.: 0 AF XY: 0.0000158 AC XY: 2AN XY: 126742
GnomAD4 exome AF: 0.00000138 AC: 2AN: 1446882Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1AN XY: 718740
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 06, 2022 | The c.2862G>C (p.E954D) alteration is located in exon 18 (coding exon 17) of the THBS1 gene. This alteration results from a G to C substitution at nucleotide position 2862, causing the glutamic acid (E) at amino acid position 954 to be replaced by an aspartic acid (D). 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