rs1713725138

Variant names:

• chr4-30722174-C-A
• rs1713725138
• NM_001173523.2:c.752C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-30722174-C-A
• chr4-30722174-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001173523.2(PCDH7):​c.752C>A​(p.Thr251Asn) 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. 13/22 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PCDH7 NM_001173523.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.11
• Publications: 0 publications found

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:58750):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20682889).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001173523.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDH7	NM_001173523.2	MANE Select	c.752C>A	p.Thr251Asn	missense	Exon 1 of 3	NP_001166994.1	A0A8Q3SI70
	PCDH7	NM_032457.4		c.752C>A	p.Thr251Asn	missense	Exon 1 of 3	NP_115833.2	A0A8V8TM73
	PCDH7	NM_002589.4		c.752C>A	p.Thr251Asn	missense	Exon 1 of 2	NP_002580.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDH7	ENST00000695919.1	MANE Select	c.752C>A	p.Thr251Asn	missense	Exon 1 of 3	ENSP00000512266.1	A0A8Q3SI70
	PCDH7	ENST00000361762.3	TSL:1	c.752C>A	p.Thr251Asn	missense	Exon 1 of 2	ENSP00000355243.2	O60245-1
	PCDH7	ENST00000621961.2	TSL:5	c.752C>A	p.Thr251Asn	missense	Exon 1 of 4	ENSP00000484874.2	A0A087X2C4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1395308 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 688148

African (AFR) AF: 0.00 AC: 0 AN: 31034

American (AMR) AF: 0.00 AC: 0 AN: 37020

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23850

East Asian (EAS) AF: 0.00 AC: 0 AN: 35794

South Asian (SAS) AF: 0.00 AC: 0 AN: 78778

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45826

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5630

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1079674

Other (OTH) AF: 0.00 AC: 0 AN: 57702

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.023	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.52	N
PhyloP100		2.1
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.12
Sift	Benign	0.19	T
Sift4G	Benign	0.62	T
Polyphen		0.95	P
Vest4		0.64
MutPred		0.24		Loss of phosphorylation at T251 (P = 0.0138)
MVP		0.35
ClinPred		0.47	T
GERP RS		5.0
PromoterAI		0.010	Neutral
Varity_R		0.18
gMVP		0.50
Mutation Taster		=11/89	disease causing

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

Other links and lift over

dbSNP: rs1713725138; hg19: chr4-30723796;