13-57633489-G-C

Position:

• chr13-57633489-G-C

Variant summary

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

The NM_001040429.3(PCDH17):​c.943G>C​(p.Gly315Arg) 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. 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: 3.52

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16693407).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH17	NM_001040429.3	c.943G>C	p.Gly315Arg	missense_variant	1/4	ENST00000377918.8	NP_001035519.1
PCDH17	XM_005266357.3	c.943G>C	p.Gly315Arg	missense_variant	2/5		XP_005266414.1
PCDH17	XM_047430276.1	c.943G>C	p.Gly315Arg	missense_variant	2/5		XP_047286232.1
PCDH17	XM_017020547.2	c.943G>C	p.Gly315Arg	missense_variant	1/4		XP_016876036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH17	ENST00000377918.8	c.943G>C	p.Gly315Arg	missense_variant	1/4	1	NM_001040429.3	ENSP00000367151	P1
	ENST00000610846.1	n.87C>G		non_coding_transcript_exon_variant	1/2	4
PCDH17	ENST00000484979.5	c.943G>C	p.Gly315Arg	missense_variant, NMD_transcript_variant	1/4	1		ENSP00000432899

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 provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2024

PCDH17: PM2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Benign	0.84
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.22
Eigen_PC	Benign	0.037
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.97	N
MutationTaster	Benign	0.98	D
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	0.49	N
REVEL	Benign	0.12
Sift	Benign	0.62	T
Sift4G	Benign	0.60	T
Polyphen		0.0030	B
Vest4		0.50
MutPred		0.35		Gain of solvent accessibility (P = 0.1319);
MVP		0.51
ClinPred		0.79	D
GERP RS		4.5
Varity_R		0.28
gMVP		0.67

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: chr13-58207623;