chr4-30721874-C-T

Variant names:

• chr4-30721874-C-T
• rs879734248
• NM_001173523.2:c.452C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001173523.2(PCDH7):​c.452C>T​(p.Thr151Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000138 in 1,449,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: PCDH7 NM_001173523.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.04

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]

ENSG00000286596 (HGNC:):

ACMG classification

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=0.2753772).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH7	NM_001173523.2	c.452C>T	p.Thr151Met	missense_variant	Exon 1 of 3	ENST00000695919.1	NP_001166994.1
PCDH7	NM_032457.4	c.452C>T	p.Thr151Met	missense_variant	Exon 1 of 3		NP_115833.2
PCDH7	NM_002589.4	c.452C>T	p.Thr151Met	missense_variant	Exon 1 of 2		NP_002580.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCDH7	ENST00000695919.1	c.452C>T	p.Thr151Met	missense_variant	Exon 1 of 3		NM_001173523.2	ENSP00000512266.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000178 AC: 4 AN: 225206 Hom.: 0 AF XY: 0.0000164 AC XY: 2 AN XY: 122122

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000597

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000299

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000138 AC: 20 AN: 1449798 Hom.: 0 Cov.: 32 AF XY: 0.0000111 AC XY: 8 AN XY: 720136

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000256

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000172

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000940 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 14, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.452C>T (p.T151M) alteration is located in exon 1 (coding exon 1) of the PCDH7 gene. This alteration results from a C to T substitution at nucleotide position 452, causing the threonine (T) at amino acid position 151 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	Uncertain	0.38
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.34
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.095	T;.
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.5	L;L
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.13
Sift	Uncertain	0.015	D;D
Sift4G	Benign	0.069	T;T
Polyphen		0.40	B;.
Vest4		0.28
MutPred		0.41		Loss of glycosylation at T151 (P = 0.0248);Loss of glycosylation at T151 (P = 0.0248);
MVP		0.43
ClinPred		0.51	D
GERP RS		5.1
Varity_R		0.13
gMVP		0.26

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

Other links and lift over

dbSNP: rs879734248; hg19: chr4-30723496;