5-141945420-G-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS1

The NM_016580.4(PCDH12):c.3516C>A(p.Gly1172=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000647 in 1,498,960 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000093 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000062 (2 hom.)
• Consequence: PCDH12 NM_016580.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.899

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 5-141945420-G-T is Benign according to our data. Variant chr5-141945420-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2889160.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.899 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0000929 (13/139962) while in subpopulation AMR AF= 0.000524 (7/13354). AF 95% confidence interval is 0.000245. There are 0 homozygotes in gnomad4. There are 8 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCDH12	NM_016580.4	c.3516C>A	p.Gly1172=	synonymous_variant	4/4	ENST00000231484.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCDH12	ENST00000231484.4	c.3516C>A	p.Gly1172=	synonymous_variant	4/4	1	NM_016580.4	P1

Frequencies

GnomAD3 genomes AF: 0.0000929 AC: 13 AN: 139876 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000243

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0103

Gnomad NFE AF: 0.0000158

Gnomad OTH AF: 0.000522

GnomAD3 exomes AF: 0.0000290 AC: 7 AN: 241572 Hom.: 0 AF XY: 0.0000535 AC XY: 7 AN XY: 130832

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000586

Gnomad ASJ exome AF: 0.000101

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000280

Gnomad OTH exome AF: 0.000169

GnomAD4 exome AF: 0.0000618 AC: 84 AN: 1358998 Hom.: 2 Cov.: 64 AF XY: 0.0000578 AC XY: 39 AN XY: 674922

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000802

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000128

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000250

Gnomad4 OTH exome AF: 0.000159

GnomAD4 genome AF: 0.0000929 AC: 13 AN: 139962 Hom.: 0 Cov.: 33 AF XY: 0.000118 AC XY: 8 AN XY: 67840

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000524

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000243

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000158

Gnomad4 OTH AF: 0.000515

Alfa AF: 0.0000678 Hom.: 0

Bravo AF: 0.0000302

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Feb 22, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	2.3
Dann	Benign	0.61

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: rs747203199; hg19: chr5-141324985;