rs17439693
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000127.3(EXT1):c.1431C>T(p.Pro477=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,611,950 control chromosomes in the GnomAD database, including 30,396 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. PS477L?) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000127.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EXT1 | NM_000127.3 | c.1431C>T | p.Pro477= | synonymous_variant | 6/11 | ENST00000378204.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EXT1 | ENST00000378204.7 | c.1431C>T | p.Pro477= | synonymous_variant | 6/11 | 1 | NM_000127.3 | P1 | |
EXT1 | ENST00000684189.1 | n.898C>T | non_coding_transcript_exon_variant | 6/11 | |||||
EXT1 | ENST00000437196.1 | c.*322C>T | 3_prime_UTR_variant, NMD_transcript_variant | 5/10 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.173 AC: 26232AN: 151990Hom.: 2556 Cov.: 32
GnomAD3 exomes AF: 0.177 AC: 44336AN: 250746Hom.: 4491 AF XY: 0.176 AC XY: 23893AN XY: 135560
GnomAD4 exome AF: 0.190 AC: 277351AN: 1459842Hom.: 27842 Cov.: 32 AF XY: 0.189 AC XY: 136972AN XY: 726332
GnomAD4 genome ? AF: 0.173 AC: 26246AN: 152108Hom.: 2554 Cov.: 32 AF XY: 0.177 AC XY: 13142AN XY: 74342
ClinVar
Submissions by phenotype
Multiple congenital exostosis Benign:2
Benign, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Exostoses, multiple, type 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at