13-57633233-C-G

Position:

• chr13-57633233-C-G

Variant summary

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

The NM_001040429.3(PCDH17):​c.687C>G​(p.Ile229Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PCDH17 NM_001040429.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.913

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCDH17	NM_001040429.3	c.687C>G	p.Ile229Met	missense_variant	1/4	ENST00000377918.8
PCDH17	XM_005266357.3	c.687C>G	p.Ile229Met	missense_variant	2/5
PCDH17	XM_047430276.1	c.687C>G	p.Ile229Met	missense_variant	2/5
PCDH17	XM_017020547.2	c.687C>G	p.Ile229Met	missense_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCDH17	ENST00000377918.8	c.687C>G	p.Ile229Met	missense_variant	1/4	1	NM_001040429.3	P1
	ENST00000610846.1	n.343G>C		non_coding_transcript_exon_variant	1/2	4
PCDH17	ENST00000484979.5	c.687C>G	p.Ile229Met	missense_variant, NMD_transcript_variant	1/4	1

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

Mar 08, 2024

The c.687C>G (p.I229M) alteration is located in exon 1 (coding exon 1) of the PCDH17 gene. This alteration results from a C to G substitution at nucleotide position 687, causing the isoleucine (I) at amino acid position 229 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	0.27
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.18	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.084
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Pathogenic	3.8	H
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.41
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.011	D
Polyphen		0.87	P
Vest4		0.70
MutPred		0.66		Gain of disorder (P = 0.062);
MVP		0.30
ClinPred		0.98	D
GERP RS		4.0
Varity_R		0.70
gMVP		0.51

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: chr13-58207367;