5-141945058-C-T

Position:

• chr5-141945058-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016580.4(PCDH12):​c.*323G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 319,448 control chromosomes in the GnomAD database, including 60,874 homozygotes. 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: 𝑓 0.63 (31811 hom., cov: 32)
  • Exomes 𝑓: 0.57 (29063 hom.)
• Consequence: PCDH12 NM_016580.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.827

Genes affected

PCDH12 (HGNC:8657): (protocadherin 12) This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. The encoded protein consists of an extracellular domain containing 6 cadherin repeats, a transmembrane domain and a cytoplasmic tail that differs from those of the classical cadherins. The gene localizes to the region on chromosome 5 where the protocadherin gene clusters reside. The exon organization of this transcript is similar to that of the gene cluster transcripts, notably the first large exon, but no significant sequence homology exists. The function of this cellular adhesion protein is undetermined but mouse protocadherin 12 does not bind catenins and appears to have no affect on cell migration or growth. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH12	NM_016580.4	c.*323G>A		3_prime_UTR_variant	4/4	ENST00000231484.4	NP_057664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH12	ENST00000231484	c.*323G>A		3_prime_UTR_variant	4/4	1	NM_016580.4	ENSP00000231484.3

Frequencies

GnomAD3 genomes AF: 0.632 AC: 95978 AN: 151958 Hom.: 31760 Cov.: 32

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.822

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.643

GnomAD4 exome AF: 0.574 AC: 96125 AN: 167372 Hom.: 29063 Cov.: 2 AF XY: 0.581 AC XY: 49956 AN XY: 86020

Gnomad4 AFR exome AF: 0.808

Gnomad4 AMR exome AF: 0.680

Gnomad4 ASJ exome AF: 0.519

Gnomad4 EAS exome AF: 0.848

Gnomad4 SAS exome AF: 0.765

Gnomad4 FIN exome AF: 0.484

Gnomad4 NFE exome AF: 0.519

Gnomad4 OTH exome AF: 0.573

GnomAD4 genome AF: 0.632 AC: 96085 AN: 152076 Hom.: 31811 Cov.: 32 AF XY: 0.635 AC XY: 47169 AN XY: 74328

Gnomad4 AFR AF: 0.815

Gnomad4 AMR AF: 0.663

Gnomad4 ASJ AF: 0.521

Gnomad4 EAS AF: 0.822

Gnomad4 SAS AF: 0.737

Gnomad4 FIN AF: 0.504

Gnomad4 NFE AF: 0.520

Gnomad4 OTH AF: 0.641

Alfa AF: 0.553 Hom.: 31890

Bravo AF: 0.649

Asia WGS AF: 0.724 AC: 2520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.56
DANN	Benign	0.39

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: rs153148; hg19: chr5-141324623;