9-95508364-TGCCGCCGCCGCC-TGCCGCC

Position:

chr9-95508364-TGCCGCCGCCGCC-TGCCGCC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_000264.5(PTCH1):c.-9_-4delGGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 1,163,744 control chromosomes in the GnomAD database, including 127 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0091 ( 11 hom., cov: 22)

Exomes 𝑓: 0.014 ( 116 hom. )

Consequence

PTCH1
NM_000264.5 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 9-95508364-TGCCGCC-T is Benign according to our data. Variant chr9-95508364-TGCCGCC-T is described in ClinVar as [Likely_benign]. Clinvar id is 193070.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-95508364-TGCCGCC-T is described in Lovd as [Likely_benign]. Variant chr9-95508364-TGCCGCC-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00908 (1343/147830) while in subpopulation SAS AF= 0.0139 (66/4750). AF 95% confidence interval is 0.0129. There are 11 homozygotes in gnomad4. There are 574 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1343 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTCH1	NM_000264.5 linkuse as main transcript	c.-9_-4delGGCGGC		5_prime_UTR_variant	1/24	ENST00000331920.11	NP_000255.2	Q13635-1
PTCH1	NM_001083603.3 linkuse as main transcript	c.199-1771_199-1766delGGCGGC		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.-9_-4delGGCGGC		5_prime_UTR_variant	1/24	5	NM_000264.5	ENSP00000332353.6		Q13635-1
PTCH1	ENST00000437951.6 linkuse as main transcript	c.199-1771_199-1766delGGCGGC		intron_variant		5	NM_001083603.3	ENSP00000389744.2		Q13635-2

Frequencies

GnomAD3 genomes

AF:

0.00910

AC:

1345

AN:

147724

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00428

Gnomad AMI

AF:

0.00112

Gnomad AMR

AF:

0.00784

Gnomad ASJ

AF:

0.0103

Gnomad EAS

AF:

0.000201

Gnomad SAS

AF:

0.0141

Gnomad FIN

AF:

0.00181

Gnomad MID

AF:

0.0226

Gnomad NFE

AF:

0.0136

Gnomad OTH

AF:

0.0109

GnomAD3 exomes

AF:

0.0141

AC:

AN:

1492

Hom.:

AF XY:

0.0174

AC XY:

AN XY:

862

show subpopulations

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0166

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0137

AC:

13923

AN:

1015914

Hom.:

116

AF XY:

0.0135

AC XY:

6505

AN XY:

480676

show subpopulations

Gnomad4 AFR exome

AF:

0.00337

Gnomad4 AMR exome

AF:

0.00680

Gnomad4 ASJ exome

AF:

0.0105

Gnomad4 EAS exome

AF:

0.0000957

Gnomad4 SAS exome

AF:

0.0119

Gnomad4 FIN exome

AF:

0.00341

Gnomad4 NFE exome

AF:

0.0146

Gnomad4 OTH exome

AF:

0.0131

GnomAD4 genome

AF:

0.00908

AC:

1343

AN:

147830

Hom.:

Cov.:

AF XY:

0.00797

AC XY:

574

AN XY:

72028

show subpopulations

Gnomad4 AFR

AF:

0.00427

Gnomad4 AMR

AF:

0.00783

Gnomad4 ASJ

AF:

0.0103

Gnomad4 EAS

AF:

0.000202

Gnomad4 SAS

AF:

0.0139

Gnomad4 FIN

AF:

0.00181

Gnomad4 NFE

AF:

0.0136

Gnomad4 OTH

AF:

0.0108

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 31, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Quest Diagnostics Nichols Institute San Juan Capistrano	May 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Nov 04, 2021	- -

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	PTCH1: BP4, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Aug 30, 2016	Variant summary: c.-9_-4delGGCGGC affects mildly conserved nucleotides, resulting in a deletion of 6 nucleotides in the 5UTR region. This variant was found in 17/5008 control chromosomes of 1000Gs project at a frequency of 0.0034, which greatly exceeds the maximal expected frequency of a pathogenic allele (0.000017). The variant has been reported as Likely Benign by one reputable databases/clinical laboratories without evidence to independently evaluate. Taking together, the variant was classified as Benign. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	Nov 03, 2021	- -

Hereditary cancer-predisposing syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 15, 2015

Co-occurence with mutation in same gene (phase unknown);In silico models in agreement (benign);Other data supporting benign classification -

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