Variant 9-95508364-TGCCGCCGCCGCC-TGCCGCCGCCGCCGCC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000264.5(PTCH1):c.-6_-4dupGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,163,256 control chromosomes in the GnomAD database, including 22,394 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4253 hom., cov: 22)

Exomes 𝑓: 0.21 ( 18141 hom. )

Consequence

PTCH1
NM_000264.5 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 3.30

Variant links:

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 links:

PTCH1 (HGNC:):

PTCH1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 9-95508364-T-TGCC is Benign according to our data. Variant chr9-95508364-T-TGCC is described in ClinVar as [Benign]. Clinvar id is 132684.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTCH1	NM_000264.5 linkuse as main transcript	c.-6_-4dupGGC		5_prime_UTR_variant	1/24	ENST00000331920.11	NP_000255.2	Q13635-1
PTCH1	NM_001083603.3 linkuse as main transcript	c.199-1768_199-1766dupGGC		intron_variant		ENST00000437951.6	NP_001077072.1	Q13635-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTCH1	ENST00000331920.11 linkuse as main transcript	c.-6_-4dupGGC		5_prime_UTR_variant	1/24	5	NM_000264.5	ENSP00000332353.6		Q13635-1
PTCH1	ENST00000437951.6 linkuse as main transcript	c.199-1768_199-1766dupGGC		intron_variant		5	NM_001083603.3	ENSP00000389744.2		Q13635-2

Frequencies

GnomAD3 genomes

AF:

0.235

AC:

34642

AN:

147642

Hom.:

4237

Cov.:

show subpopulations

Gnomad AFR

AF:

0.280

Gnomad AMI

AF:

0.201

Gnomad AMR

AF:

0.147

Gnomad ASJ

AF:

0.292

Gnomad EAS

AF:

0.228

Gnomad SAS

AF:

0.165

Gnomad FIN

AF:

0.258

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.227

Gnomad OTH

AF:

0.219

GnomAD3 exomes

AF:

0.119

AC:

177

AN:

1492

Hom.:

AF XY:

0.117

AC XY:

101

AN XY:

862

show subpopulations

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0500

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0313

Gnomad NFE exome

AF:

0.129

Gnomad OTH exome

AF:

0.211

GnomAD4 exome

AF:

0.205

AC:

208647

AN:

1015512

Hom.:

18141

Cov.:

AF XY:

0.205

AC XY:

98564

AN XY:

480486

show subpopulations

Gnomad4 AFR exome

AF:

0.261

Gnomad4 AMR exome

AF:

0.0920

Gnomad4 ASJ exome

AF:

0.234

Gnomad4 EAS exome

AF:

0.151

Gnomad4 SAS exome

AF:

0.166

Gnomad4 FIN exome

AF:

0.176

Gnomad4 NFE exome

AF:

0.208

Gnomad4 OTH exome

AF:

0.197

GnomAD4 genome

AF:

0.235

AC:

34683

AN:

147744

Hom.:

4253

Cov.:

AF XY:

0.233

AC XY:

16780

AN XY:

71992

show subpopulations

Gnomad4 AFR

AF:

0.280

Gnomad4 AMR

AF:

0.146

Gnomad4 ASJ

AF:

0.292

Gnomad4 EAS

AF:

0.227

Gnomad4 SAS

AF:

0.166

Gnomad4 FIN

AF:

0.258

Gnomad4 NFE

AF:

0.227

Gnomad4 OTH

AF:

0.226

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Aug 30, 2016	Variant summary: c.-6_-4dupGGC affects mildly conserved nucleotides, resulting in duplication of 3 nucleotides in the 5UTR region. This variant was found in 1014/5008 control chromosomes of 1000Gs project at a frequency of 0.2024, which greatly exceeds the maximal expected frequency of a pathogenic allele (0.000017). The variant has been reported as Benign by several reputable databases/clinical laboratories without evidence to independently evaluate. Taking together, based on the prevalence in the general population, the variant was classified as Benign. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	-	- -
Benign, flagged submission	clinical testing	Quest Diagnostics Nichols Institute San Juan Capistrano	May 24, 2021	- -
Likely benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 25, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Quest Diagnostics Nichols Institute San Juan Capistrano	May 24, 2021	- -

PTCH1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 08, 2024

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Gorlin syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 31, 2016

- -

Hereditary cancer-predisposing syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 2020

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over