NM_000264.5:c.46_51delGGCGGC
Variant summary
Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP3BP6BS2
The NM_000264.5(PTCH1):c.46_51delGGCGGC(p.Gly16_Gly17del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,399,318 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. G16G) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000019 ( 0 hom. )
Consequence
PTCH1
NM_000264.5 conservative_inframe_deletion
NM_000264.5 conservative_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.27
Publications
5 publications found
Genes affected
PTCH1 (HGNC:9585): (patched 1) This gene encodes a member of the patched family of proteins and a component of the hedgehog signaling pathway. Hedgehog signaling is important in embryonic development and tumorigenesis. The encoded protein is the receptor for the secreted hedgehog ligands, which include sonic hedgehog, indian hedgehog and desert hedgehog. Following binding by one of the hedgehog ligands, the encoded protein is trafficked away from the primary cilium, relieving inhibition of the G-protein-coupled receptor smoothened, which results in activation of downstream signaling. Mutations of this gene have been associated with basal cell nevus syndrome and holoprosencephaly. [provided by RefSeq, Aug 2017]
PTCH1 Gene-Disease associations (from GenCC):
- basal cell nevus syndrome 1Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
- holoprosencephaly 7Inheritance: AD Classification: DEFINITIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
- nevoid basal cell carcinoma syndromeInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet
- holoprosencephalyInheritance: AD Classification: LIMITED Submitted by: Illumina
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -6 ACMG points.
BP3
Nonframeshift variant in repetitive region in NM_000264.5
BP6
Variant 9-95508310-TGCCGCC-T is Benign according to our data. Variant chr9-95508310-TGCCGCC-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 1103077.
BS2
High AC in GnomAdExome4 at 24 AD gene.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000264.5. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PTCH1 | NM_000264.5 | MANE Select | c.46_51delGGCGGC | p.Gly16_Gly17del | conservative_inframe_deletion | Exon 1 of 24 | NP_000255.2 | ||
| PTCH1 | NM_001083603.3 | MANE Plus Clinical | c.199-1717_199-1712delGGCGGC | intron | N/A | NP_001077072.1 | |||
| PTCH1 | NM_001354918.2 | c.46_51delGGCGGC | p.Gly16_Gly17del | conservative_inframe_deletion | Exon 1 of 23 | NP_001341847.1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PTCH1 | ENST00000331920.11 | TSL:5 MANE Select | c.46_51delGGCGGC | p.Gly16_Gly17del | conservative_inframe_deletion | Exon 1 of 24 | ENSP00000332353.6 | ||
| PTCH1 | ENST00000437951.6 | TSL:5 MANE Plus Clinical | c.199-1717_199-1712delGGCGGC | intron | N/A | ENSP00000389744.2 | |||
| PTCH1 | ENST00000468211.6 | TSL:1 | c.4-1717_4-1712delGGCGGC | intron | N/A | ENSP00000449745.1 |
Frequencies
GnomAD3 genomes 0.0000133 AC: 2AN: 150744Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
2
AN:
150744
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.00 AC: 0AN: 21730 AF XY: 0.00
GnomAD2 exomes
AF:
AC:
0
AN:
21730
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000192 AC: 24AN: 1248574Hom.: 0 AF XY: 0.0000148 AC XY: 9AN XY: 608970 show subpopulations
GnomAD4 exome
AF:
AC:
24
AN:
1248574
Hom.:
AF XY:
AC XY:
9
AN XY:
608970
show subpopulations
African (AFR)
AF:
AC:
0
AN:
24394
American (AMR)
AF:
AC:
0
AN:
14198
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
17570
East Asian (EAS)
AF:
AC:
0
AN:
28922
South Asian (SAS)
AF:
AC:
0
AN:
57180
European-Finnish (FIN)
AF:
AC:
0
AN:
35786
Middle Eastern (MID)
AF:
AC:
0
AN:
3536
European-Non Finnish (NFE)
AF:
AC:
23
AN:
1015750
Other (OTH)
AF:
AC:
1
AN:
51238
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.506
Heterozygous variant carriers
0
1
3
4
6
7
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome 0.0000133 AC: 2AN: 150744Hom.: 0 Cov.: 32 AF XY: 0.0000136 AC XY: 1AN XY: 73570 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
2
AN:
150744
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
73570
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
1
AN:
41214
American (AMR)
AF:
AC:
0
AN:
15192
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3450
East Asian (EAS)
AF:
AC:
0
AN:
5108
South Asian (SAS)
AF:
AC:
0
AN:
4798
European-Finnish (FIN)
AF:
AC:
0
AN:
10186
Middle Eastern (MID)
AF:
AC:
0
AN:
312
European-Non Finnish (NFE)
AF:
AC:
1
AN:
67510
Other (OTH)
AF:
AC:
0
AN:
2064
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.350
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Conflicting classifications of pathogenicity
Revision:criteria provided, conflicting classifications
Pathogenic
VUS
Benign
Condition
-
-
1
Gorlin syndrome (1)
-
-
1
Hereditary cancer-predisposing syndrome (1)
-
1
-
not provided (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.