Variant rs164077 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_016580.4(PCDH12):c.192T>C(p.Ala64=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 1,613,928 control chromosomes in the GnomAD database, including 516,978 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.73 ( 42083 hom., cov: 32)

Exomes 𝑓: 0.80 ( 474895 hom. )

Consequence

PCDH12
NM_016580.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.711

Variant links:

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 links:

RNF14 (HGNC:):

RNF14 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 5-141957660-A-G is Benign according to our data. Variant chr5-141957660-A-G is described in ClinVar as [Benign]. Clinvar id is 1168162.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.711 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PCDH12	NM_016580.4 linkuse as main transcript	c.192T>C	p.Ala64=	synonymous_variant	1/4	ENST00000231484.4
RNF14	XM_047417904.1 linkuse as main transcript	c.-181+8250A>G		intron_variant
RNF14	XM_047417908.1 linkuse as main transcript	c.-181+8250A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCDH12	ENST00000231484.4 linkuse as main transcript	c.192T>C	p.Ala64=	synonymous_variant	1/4	1	NM_016580.4	P1

Frequencies

GnomAD3 genomes

AF:

0.731

AC:

111165

AN:

151984

Hom.:

42062

Cov.:

show subpopulations

Gnomad AFR

AF:

0.520

Gnomad AMI

AF:

0.760

Gnomad AMR

AF:

0.802

Gnomad ASJ

AF:

0.742

Gnomad EAS

AF:

0.966

Gnomad SAS

AF:

0.826

Gnomad FIN

AF:

0.810

Gnomad MID

AF:

0.712

Gnomad NFE

AF:

0.805

Gnomad OTH

AF:

0.758

GnomAD3 exomes

AF:

0.808

AC:

202808

AN:

251098

Hom.:

83059

AF XY:

0.812

AC XY:

110220

AN XY:

135784

show subpopulations

Gnomad AFR exome

AF:

0.506

Gnomad AMR exome

AF:

0.877

Gnomad ASJ exome

AF:

0.748

Gnomad EAS exome

AF:

0.965

Gnomad SAS exome

AF:

0.837

Gnomad FIN exome

AF:

0.813

Gnomad NFE exome

AF:

0.801

Gnomad OTH exome

AF:

0.792

GnomAD4 exome

AF:

0.804

AC:

1174995

AN:

1461826

Hom.:

474895

Cov.:

AF XY:

0.805

AC XY:

585540

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.513

Gnomad4 AMR exome

AF:

0.869

Gnomad4 ASJ exome

AF:

0.747

Gnomad4 EAS exome

AF:

0.973

Gnomad4 SAS exome

AF:

0.835

Gnomad4 FIN exome

AF:

0.814

Gnomad4 NFE exome

AF:

0.803

Gnomad4 OTH exome

AF:

0.791

GnomAD4 genome

AF:

0.731

AC:

111226

AN:

152102

Hom.:

42083

Cov.:

AF XY:

0.737

AC XY:

54826

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.520

Gnomad4 AMR

AF:

0.803

Gnomad4 ASJ

AF:

0.742

Gnomad4 EAS

AF:

0.966

Gnomad4 SAS

AF:

0.826

Gnomad4 FIN

AF:

0.810

Gnomad4 NFE

AF:

0.805

Gnomad4 OTH

AF:

0.755

Alfa

AF:

0.772

Hom.:

27986

Bravo

AF:

0.720

Asia WGS

AF:

0.840

AC:

2921

AN:

3478

EpiCase

AF:

0.794

EpiControl

AF:

0.791

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 04, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Diencephalic-mesencephalic junction dysplasia syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.0

DANN

Benign

0.65

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over