4-30721874-C-G

Variant names:

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

Variant summary

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

The NM_001173523.2(PCDH7):​c.452C>G​(p.Thr151Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000069 in 1,449,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PCDH7 NM_001173523.2 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.31900427).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH7	NM_001173523.2	c.452C>G	p.Thr151Arg	missense_variant	Exon 1 of 3	ENST00000695919.1	NP_001166994.1
PCDH7	NM_032457.4	c.452C>G	p.Thr151Arg	missense_variant	Exon 1 of 3		NP_115833.2
PCDH7	NM_002589.4	c.452C>G	p.Thr151Arg	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>G	p.Thr151Arg	missense_variant	Exon 1 of 3		NM_001173523.2	ENSP00000512266.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000444 AC: 1 AN: 225206 Hom.: 0 AF XY: 0.00000819 AC XY: 1 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: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000998

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449798 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 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: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.03e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.080	T;.
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.32	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.45	N;N
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.20
Sift	Uncertain	0.0050	D;D
Sift4G	Uncertain	0.020	D;D
Polyphen		0.77	P;.
Vest4		0.41
MutPred		0.47		Loss of glycosylation at T151 (P = 0.0248);Loss of glycosylation at T151 (P = 0.0248);
MVP		0.45
ClinPred		0.65	D
GERP RS		5.1
Varity_R		0.41
gMVP		0.45

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;