NM_016580.4:c.*323G>C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016580.4(PCDH12):​c.*323G>C variant causes a 3 prime UTR 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH12	NM_016580.4	c.*323G>C		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>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_016580.4	ENSP00000231484.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 168028 Hom.: 0 Cov.: 2 AF XY: 0.00 AC XY: 0 AN XY: 86348

African (AFR) AF: 0.00 AC: 0 AN: 5116

American (AMR) AF: 0.00 AC: 0 AN: 6646

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5728

East Asian (EAS) AF: 0.00 AC: 0 AN: 10940

South Asian (SAS) AF: 0.00 AC: 0 AN: 11552

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9862

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 814

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 106750

Other (OTH) AF: 0.00 AC: 0 AN: 10620

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.45
DANN	Benign	0.42
PhyloP100		-0.83

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;