rs374924167
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_000264.5(PTCH1):c.1710G>T(p.Leu570=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000787 in 1,614,036 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 Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L570L) has been classified as Likely benign.
Frequency
Consequence
NM_000264.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -15 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTCH1 | NM_000264.5 | c.1710G>T | p.Leu570= | synonymous_variant | 12/24 | ENST00000331920.11 | |
PTCH1 | NM_001083603.3 | c.1707G>T | p.Leu569= | synonymous_variant | 12/24 | ENST00000437951.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.1710G>T | p.Leu570= | synonymous_variant | 12/24 | 5 | NM_000264.5 | A2 | |
PTCH1 | ENST00000437951.6 | c.1707G>T | p.Leu569= | synonymous_variant | 12/24 | 5 | NM_001083603.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152196Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000876 AC: 22AN: 251196Hom.: 0 AF XY: 0.000110 AC XY: 15AN XY: 135766
GnomAD4 exome AF: 0.0000814 AC: 119AN: 1461722Hom.: 0 Cov.: 31 AF XY: 0.0000770 AC XY: 56AN XY: 727164
GnomAD4 genome ? AF: 0.0000525 AC: 8AN: 152314Hom.: 0 Cov.: 32 AF XY: 0.0000268 AC XY: 2AN XY: 74492
ClinVar
Submissions by phenotype
Gorlin syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
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. - |
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Jan 08, 2022 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 04, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Holoprosencephaly 7 Benign:1
Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at