9-95516658-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001083603.3(PTCH1):​c.163G>A​(p.Asp55Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D55H) has been classified as Benign.

Frequency

Genomes: not found (cov: 31)

Consequence

PTCH1
NM_001083603.3 missense

Scores

1
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.92
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.20746836).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PTCH1NM_001083603.3 linkc.163G>A p.Asp55Asn missense_variant Exon 1 of 24 ENST00000437951.6 NP_001077072.1 Q13635-2
PTCH1NM_001083602.3 linkc.-187G>A 5_prime_UTR_variant Exon 1 of 24 NP_001077071.1 Q13635-3
PTCH1NM_001354919.2 linkc.-187G>A 5_prime_UTR_variant Exon 1 of 5 NP_001341848.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PTCH1ENST00000437951.6 linkc.163G>A p.Asp55Asn missense_variant Exon 1 of 24 5 NM_001083603.3 ENSP00000389744.2 Q13635-2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
15
DANN
Benign
0.81
Eigen
Benign
-0.72
Eigen_PC
Benign
-0.74
FATHMM_MKL
Benign
0.24
N
LIST_S2
Benign
0.33
T
M_CAP
Pathogenic
0.87
D
MetaRNN
Benign
0.21
T
MetaSVM
Benign
-0.30
T
PROVEAN
Benign
-0.010
N
REVEL
Benign
0.18
Sift
Benign
0.30
T
Sift4G
Benign
0.67
T
Polyphen
0.0030
B
Vest4
0.26
MutPred
0.15
Loss of solvent accessibility (P = 0.01);
MVP
0.38
ClinPred
0.11
T
GERP RS
3.1

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-98278940; API