chr4-30722174-C-T

Variant names:

• chr4-30722174-C-T
• rs1713725138
• NM_001173523.2:c.752C>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>T​(p.Thr251Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000043 in 1,395,310 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T251N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: PCDH7 NM_001173523.2 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.137692).

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>T	p.Thr251Ile	missense	Exon 1 of 3	NP_001166994.1	A0A8Q3SI70
	PCDH7	NM_032457.4		c.752C>T	p.Thr251Ile	missense	Exon 1 of 3	NP_115833.2	A0A8V8TM73
	PCDH7	NM_002589.4		c.752C>T	p.Thr251Ile	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>T	p.Thr251Ile	missense	Exon 1 of 3	ENSP00000512266.1	A0A8Q3SI70
	PCDH7	ENST00000361762.3	TSL:1	c.752C>T	p.Thr251Ile	missense	Exon 1 of 2	ENSP00000355243.2	O60245-1
	PCDH7	ENST00000621961.2	TSL:5	c.752C>T	p.Thr251Ile	missense	Exon 1 of 4	ENSP00000484874.2	A0A087X2C4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000430 AC: 6 AN: 1395310 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 688150

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: 23852

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: 0.00000556 AC: 6 AN: 1079674

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.10
Eigen_PC	Benign	0.042
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.92	L
PhyloP100		2.1
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.24
Sift	Benign	0.053	T
Sift4G	Benign	0.18	T
Polyphen		0.20	B
Vest4		0.32
MutPred		0.43		Loss of phosphorylation at T251 (P = 0.0138)
MVP		0.30
ClinPred		0.42	T
GERP RS		5.0
PromoterAI		0.022	Neutral
Varity_R		0.27
gMVP		0.57
Mutation Taster		=16/84	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;