NM_001173523.2:c.112C>A

Variant names:

• chr4-30721534-C-A
• rs143147908
• NM_001173523.2:c.112C>A

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.112C>A​(p.Leu38Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000312 in 1,601,014 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: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: PCDH7 NM_001173523.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.462
• 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=0.22792882).

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.112C>A	p.Leu38Met	missense	Exon 1 of 3	NP_001166994.1	A0A8Q3SI70
	PCDH7	NM_032457.4		c.112C>A	p.Leu38Met	missense	Exon 1 of 3	NP_115833.2	A0A8V8TM73
	PCDH7	NM_002589.4		c.112C>A	p.Leu38Met	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.112C>A	p.Leu38Met	missense	Exon 1 of 3	ENSP00000512266.1	A0A8Q3SI70
	PCDH7	ENST00000361762.3	TSL:1	c.112C>A	p.Leu38Met	missense	Exon 1 of 2	ENSP00000355243.2	O60245-1
	PCDH7	ENST00000621961.2	TSL:5	c.112C>A	p.Leu38Met	missense	Exon 1 of 4	ENSP00000484874.2	A0A087X2C4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152222 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000276 AC: 4 AN: 1448792 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 721110

African (AFR) AF: 0.000120 AC: 4 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44642

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26080

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.00 AC: 0 AN: 86176

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111514

Other (OTH) AF: 0.00 AC: 0 AN: 60132

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152222 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74350

African (AFR) AF: 0.0000241 AC: 1 AN: 41478

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ESP6500AA AF: 0.000231 AC: 1

ESP6500EA AF: 0.00 AC: 0

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	0.28
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.052	T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.070	N
PhyloP100		0.46
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.099
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.87	P
Vest4		0.35
MVP		0.25
ClinPred		0.70	D
GERP RS		2.8
Varity_R		0.29
gMVP		0.59
Mutation Taster		=90/10	polymorphism

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: rs143147908; hg19: chr4-30723156;