NM_000264.5:c.2183C>T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000264.5(PTCH1):c.2183C>T(p.Thr728Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,614,146 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000264.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
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PTCH1 | ENST00000331920.11 | c.2183C>T | p.Thr728Met | missense_variant | Exon 14 of 24 | 5 | NM_000264.5 | ENSP00000332353.6 | ||
PTCH1 | ENST00000437951.6 | c.2180C>T | p.Thr727Met | missense_variant | Exon 14 of 24 | 5 | NM_001083603.3 | ENSP00000389744.2 |
Frequencies
GnomAD3 genomes AF: 0.00617 AC: 939AN: 152140Hom.: 14 Cov.: 32
GnomAD3 exomes AF: 0.00159 AC: 399AN: 251490Hom.: 3 AF XY: 0.00118 AC XY: 161AN XY: 135918
GnomAD4 exome AF: 0.000596 AC: 872AN: 1461888Hom.: 5 Cov.: 33 AF XY: 0.000502 AC XY: 365AN XY: 727246
GnomAD4 genome AF: 0.00617 AC: 940AN: 152258Hom.: 14 Cov.: 32 AF XY: 0.00565 AC XY: 421AN XY: 74452
ClinVar
Submissions by phenotype
not specified Benign:5Other:1
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not provided Uncertain:1Benign:4
PTCH1: BS1, BS2 -
This variant is associated with the following publications: (PMID: 11941477, 20981092, 17096318, 22703879, 24728327) -
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Holoprosencephaly 7 Pathogenic:1Benign:1
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This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Gorlin syndrome Benign:2
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
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Hereditary cancer-predisposing syndrome Benign:2
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This alteration is classified as 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. -
Gorlin syndrome;C1835820:Holoprosencephaly 7;C2751544:Basal cell carcinoma, susceptibility to, 1 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at