4-30722597-A-C

Position:

• chr4-30722597-A-C

Variant summary

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

The NM_001173523.2(PCDH7):​c.1175A>C​(p.Gln392Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PCDH7 NM_001173523.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.25

Genes affected

PCDH7 (HGNC:8659): (protocadherin 7) This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. The gene encodes a protein with an extracellular domain containing 7 cadherin repeats. The gene product is an integral membrane protein that is thought to function in cell-cell recognition and adhesion. Alternative splicing yields isoforms with unique cytoplasmic tails. [provided by RefSeq, Jul 2008]

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=0.20453879).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCDH7	NM_001173523.2	c.1175A>C	p.Gln392Pro	missense_variant	1/3	ENST00000695919.1
PCDH7	NM_032457.4	c.1175A>C	p.Gln392Pro	missense_variant	1/3
PCDH7	NM_002589.4	c.1175A>C	p.Gln392Pro	missense_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCDH7	ENST00000695919.1	c.1175A>C	p.Gln392Pro	missense_variant	1/3		NM_001173523.2	A1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

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

Jun 18, 2021

The c.1175A>C (p.Q392P) alteration is located in exon 1 (coding exon 1) of the PCDH7 gene. This alteration results from a A to C substitution at nucleotide position 1175, causing the glutamine (Q) at amino acid position 392 to be replaced by a proline (P). 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	Pathogenic	0.72
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Benign	0.94
DEOGEN2	Benign	0.023	T;.
Eigen	Benign	-0.15
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.68	N;N
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	0.69	N;N
REVEL	Benign	0.21
Sift	Benign	0.17	T;T
Sift4G	Benign	0.33	T;T
Polyphen		0.0	B;.
Vest4		0.39
MutPred		0.48		Gain of glycosylation at Q392 (P = 0.0056);Gain of glycosylation at Q392 (P = 0.0056);
MVP		0.44
ClinPred		0.55	D
GERP RS		5.5
Varity_R		0.23
gMVP		0.71

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: chr4-30724219;