Variant 12-8921663-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_004426.3(PHC1):c.369C>T(p.Pro123Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 1,612,636 control chromosomes in the GnomAD database, including 401,628 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 30799 hom., cov: 30)

Exomes 𝑓: 0.71 ( 370829 hom. )

Consequence

PHC1
NM_004426.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.02

Variant links:

Genes affected

PHC1 (HGNC:3182): (polyhomeotic homolog 1) This gene is a homolog of the Drosophila polyhomeotic gene, which is a member of the Polycomb group of genes. The gene product is a component of a multimeric protein complex that contains EDR2 and the vertebrate Polycomb protein BMH1. The gene product, the EDR2 protein, and the Drosophila polyhomeotic protein share 2 highly conserved domains, named homology domains I and II. These domains are involved in protein-protein interactions and may mediate heterodimerization of the protein encoded by this gene and the EDR2 protein. [provided by RefSeq, Jul 2008]

PHC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 12-8921663-C-T is Benign according to our data. Variant chr12-8921663-C-T is described in ClinVar as [Benign]. Clinvar id is 1252581.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.02 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHC1	NM_004426.3 link	c.369C>T	p.Pro123Pro	synonymous_variant	5/15	ENST00000544916.6	NP_004417.2	P78364Q6GMQ3Q6N083

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHC1	ENST00000544916.6 link	c.369C>T	p.Pro123Pro	synonymous_variant	5/15	1	NM_004426.3	ENSP00000437659.1		P78364

Frequencies

GnomAD3 genomes

AF:

0.624

AC:

94684

AN:

151800

Hom.:

30797

Cov.:

show subpopulations

Gnomad AFR

AF:

0.431

Gnomad AMI

AF:

0.635

Gnomad AMR

AF:

0.604

Gnomad ASJ

AF:

0.803

Gnomad EAS

AF:

0.723

Gnomad SAS

AF:

0.832

Gnomad FIN

AF:

0.665

Gnomad MID

AF:

0.775

Gnomad NFE

AF:

0.706

Gnomad OTH

AF:

0.650

GnomAD3 exomes

AF:

0.694

AC:

174055

AN:

250648

Hom.:

61584

AF XY:

0.710

AC XY:

96156

AN XY:

135512

show subpopulations

Gnomad AFR exome

AF:

0.426

Gnomad AMR exome

AF:

0.620

Gnomad ASJ exome

AF:

0.799

Gnomad EAS exome

AF:

0.721

Gnomad SAS exome

AF:

0.831

Gnomad FIN exome

AF:

0.664

Gnomad NFE exome

AF:

0.709

Gnomad OTH exome

AF:

0.726

GnomAD4 exome

AF:

0.710

AC:

1036883

AN:

1460718

Hom.:

370829

Cov.:

AF XY:

0.715

AC XY:

519665

AN XY:

726756

show subpopulations

Gnomad4 AFR exome

AF:

0.425

Gnomad4 AMR exome

AF:

0.619

Gnomad4 ASJ exome

AF:

0.798

Gnomad4 EAS exome

AF:

0.727

Gnomad4 SAS exome

AF:

0.831

Gnomad4 FIN exome

AF:

0.659

Gnomad4 NFE exome

AF:

0.712

Gnomad4 OTH exome

AF:

0.710

GnomAD4 genome

AF:

0.623

AC:

94716

AN:

151918

Hom.:

30799

Cov.:

AF XY:

0.622

AC XY:

46207

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.430

Gnomad4 AMR

AF:

0.604

Gnomad4 ASJ

AF:

0.803

Gnomad4 EAS

AF:

0.724

Gnomad4 SAS

AF:

0.831

Gnomad4 FIN

AF:

0.665

Gnomad4 NFE

AF:

0.706

Gnomad4 OTH

AF:

0.649

Alfa

AF:

0.672

Hom.:

15202

Bravo

AF:

0.608

Asia WGS

AF:

0.741

AC:

2577

AN:

3478

EpiCase

AF:

0.718

EpiControl

AF:

0.726

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -

Microcephaly 11, primary, autosomal recessive

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

-0.38

CADD

Benign

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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