13-57633042-C-A

Position:

• chr13-57633042-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001040429.3(PCDH17):​c.496C>A​(p.Leu166Ile) 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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PCDH17 NM_001040429.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.33

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]

ENSG00000278722 (HGNC:):

ACMG classification

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=0.20002428).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH17	NM_001040429.3	c.496C>A	p.Leu166Ile	missense_variant	1/4	ENST00000377918.8	NP_001035519.1
PCDH17	XM_005266357.3	c.496C>A	p.Leu166Ile	missense_variant	2/5		XP_005266414.1
PCDH17	XM_047430276.1	c.496C>A	p.Leu166Ile	missense_variant	2/5		XP_047286232.1
PCDH17	XM_017020547.2	c.496C>A	p.Leu166Ile	missense_variant	1/4		XP_016876036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH17	ENST00000377918.8	c.496C>A	p.Leu166Ile	missense_variant	1/4	1	NM_001040429.3	ENSP00000367151.3
PCDH17	ENST00000484979.5	n.496C>A		non_coding_transcript_exon_variant	1/4	1		ENSP00000432899.1
ENSG00000278722	ENST00000610846.1	n.522+12G>T		intron_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 21, 2024

The c.496C>A (p.L166I) alteration is located in exon 1 (coding exon 1) of the PCDH17 gene. This alteration results from a C to A substitution at nucleotide position 496, causing the leucine (L) at amino acid position 166 to be replaced by an isoleucine (I). 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	0.13
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Benign	0.90
DEOGEN2	Benign	0.045	T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.047
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.88	L
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.12
Sift	Benign	0.24	T
Sift4G	Benign	0.30	T
Polyphen		0.053	B
Vest4		0.34
MutPred		0.56		Gain of catalytic residue at A161 (P = 0.004);
MVP		0.30
ClinPred		0.72	D
GERP RS		4.8
Varity_R		0.35
gMVP		0.091

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-58207176;