rs376844749
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 5P and 4B. PM1PP2PP3_ModerateBS2
The NM_000264.5(PTCH1):c.3422C>T(p.Ala1141Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 1,613,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A1141A) has been classified as Likely benign.
Frequency
Consequence
NM_000264.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTCH1 | NM_000264.5 | c.3422C>T | p.Ala1141Val | missense_variant | 20/24 | ENST00000331920.11 | |
PTCH1 | NM_001083603.3 | c.3419C>T | p.Ala1140Val | missense_variant | 20/24 | ENST00000437951.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.3422C>T | p.Ala1141Val | missense_variant | 20/24 | 5 | NM_000264.5 | A2 | |
PTCH1 | ENST00000437951.6 | c.3419C>T | p.Ala1140Val | missense_variant | 20/24 | 5 | NM_001083603.3 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152150Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251306Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135864
GnomAD4 exome AF: 0.0000328 AC: 48AN: 1461772Hom.: 0 Cov.: 31 AF XY: 0.0000261 AC XY: 19AN XY: 727198
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152150Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74324
ClinVar
Submissions by phenotype
Gorlin syndrome Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 14, 2024 | - - |
Uncertain significance, no assertion criteria provided | research | CSER _CC_NCGL, University of Washington | Jun 01, 2014 | - - |
Basal cell carcinoma, susceptibility to, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Sep 24, 2022 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 24, 2024 | The p.A1141V variant (also known as c.3422C>T), located in coding exon 20 of the PTCH1 gene, results from a C to T substitution at nucleotide position 3422. The alanine at codon 1141 is replaced by valine, an amino acid with similar properties. This alteration was identified in a patient suspected of having nevoid basal cell carcinoma syndrome due to her history of multiple basal cell carcinomas and two meningiomas (Brellier F et al. Br. J. Dermatol. 2008 Aug;159:445-52). This variant has been seen in an exome cohort and was classified as a variant of unknown significance by authors (Amendola LM et al. Genome Res. 2015 Mar;25:305-15). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at