5-141945058-C-T

Variant names:

• chr5-141945058-C-T
• rs153148
• NM_016580.4:c.*323G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

PCDH12 Gene-Disease associations (from GenCC):

• diencephalic-mesencephalic junction dysplasia syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• diencephalic-mesencephalic junction dysplasia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PCDH12	NM_016580.4	c.*323G>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000231484.4	NP_057664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCDH12	ENST00000231484.4	c.*323G>A		3_prime_UTR_variant	Exon 4 of 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

African (AFR) AF: 0.808 AC: 4130 AN: 5110

American (AMR) AF: 0.680 AC: 4508 AN: 6628

Ashkenazi Jewish (ASJ) AF: 0.519 AC: 2957 AN: 5698

East Asian (EAS) AF: 0.848 AC: 9254 AN: 10908

South Asian (SAS) AF: 0.765 AC: 8815 AN: 11528

European-Finnish (FIN) AF: 0.484 AC: 4748 AN: 9804

Middle Eastern (MID) AF: 0.606 AC: 491 AN: 810

European-Non Finnish (NFE) AF: 0.519 AC: 55161 AN: 106310

Other (OTH) AF: 0.573 AC: 6061 AN: 10576

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

African (AFR) AF: 0.815 AC: 33832 AN: 41496

American (AMR) AF: 0.663 AC: 10121 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 1809 AN: 3470

East Asian (EAS) AF: 0.822 AC: 4234 AN: 5150

South Asian (SAS) AF: 0.737 AC: 3555 AN: 4826

European-Finnish (FIN) AF: 0.504 AC: 5328 AN: 10580

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.520 AC: 35370 AN: 67966

Other (OTH) AF: 0.641 AC: 1355 AN: 2114

Alfa AF: 0.559 Hom.: 42708

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
PhyloP100		-0.83
Mutation Taster		=100/0	polymorphism (auto)

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: rs153148; hg19: chr5-141324623;