Variant 13-57632665-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001040429.3(PCDH17):c.119G>T(p.Arg40Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PCDH17
NM_001040429.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.30

Variant links:

Genes affected

PCDH17 (HGNC:14267): (protocadherin 17) This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. The encoded protein contains six extracellular cadherin domains, a transmembrane domain, and a cytoplasmic tail differing from those of the classical cadherins. The encoded protein may play a role in the establishment and function of specific cell-cell connections in the brain. [provided by RefSeq, Jul 2008]

PCDH17 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34590816).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PCDH17	NM_001040429.3 linkuse as main transcript	c.119G>T	p.Arg40Met	missense_variant	1/4	ENST00000377918.8	NP_001035519.1
PCDH17	XM_005266357.3 linkuse as main transcript	c.119G>T	p.Arg40Met	missense_variant	2/5		XP_005266414.1
PCDH17	XM_047430276.1 linkuse as main transcript	c.119G>T	p.Arg40Met	missense_variant	2/5		XP_047286232.1
PCDH17	XM_017020547.2 linkuse as main transcript	c.119G>T	p.Arg40Met	missense_variant	1/4		XP_016876036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH17	ENST00000377918.8 linkuse as main transcript	c.119G>T	p.Arg40Met	missense_variant	1/4	1	NM_001040429.3	ENSP00000367151	P1	O14917-1
PCDH17	ENST00000484979.5 linkuse as main transcript	c.119G>T	p.Arg40Met	missense_variant, NMD_transcript_variant	1/4	1		ENSP00000432899		O14917-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000810

AC:

AN:

247056

Hom.:

AF XY:

0.00000745

AC XY:

AN XY:

134302

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459828

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726322

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000389

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 16, 2022

The c.119G>T (p.R40M) alteration is located in exon 1 (coding exon 1) of the PCDH17 gene. This alteration results from a G to T substitution at nucleotide position 119, causing the arginine (R) at amino acid position 40 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.064

Eigen

Benign

0.057

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.82

M_CAP

Benign

0.070

MetaRNN

Benign

0.35

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.7

MutationTaster

Benign

0.53

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.7

REVEL

Benign

0.13

Sift

Uncertain

0.010

Sift4G

Uncertain

0.010

Polyphen

0.74

Vest4

0.35

MVP

0.33

ClinPred

0.87

GERP RS

4.3

Varity_R

0.45

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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