Variant chr12-8930740-A-G 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_004426.3(PHC1):c.918A>G(p.Arg306=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.86 ( 54764 hom., cov: 20)

Exomes 𝑓: 0.93 ( 467421 hom. )

Failed GnomAD Quality Control

Consequence

PHC1
NM_004426.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.08

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:

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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=-0.59).

BP6

Variant 12-8930740-A-G is Benign according to our data. Variant chr12-8930740-A-G is described in ClinVar as [Benign]. Clinvar id is 211899.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.08 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHC1	NM_004426.3 linkuse as main transcript	c.918A>G	p.Arg306=	synonymous_variant	7/15	ENST00000544916.6	NP_004417.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHC1	ENST00000544916.6 linkuse as main transcript	c.918A>G	p.Arg306=	synonymous_variant	7/15	1	NM_004426.3	ENSP00000437659	P1

Frequencies

GnomAD3 genomes

AF:

0.855

AC:

124731

AN:

145816

Hom.:

54741

Cov.:

show subpopulations

Gnomad AFR

AF:

0.645

Gnomad AMI

AF:

0.950

Gnomad AMR

AF:

0.900

Gnomad ASJ

AF:

0.942

Gnomad EAS

AF:

0.782

Gnomad SAS

AF:

0.964

Gnomad FIN

AF:

0.968

Gnomad MID

AF:

0.916

Gnomad NFE

AF:

0.946

Gnomad OTH

AF:

0.858

GnomAD3 exomes

AF:

0.860

AC:

107968

AN:

125610

Hom.:

50561

AF XY:

0.870

AC XY:

56469

AN XY:

64878

show subpopulations

Gnomad AFR exome

AF:

0.482

Gnomad AMR exome

AF:

0.900

Gnomad ASJ exome

AF:

0.864

Gnomad EAS exome

AF:

0.717

Gnomad SAS exome

AF:

0.939

Gnomad FIN exome

AF:

0.945

Gnomad NFE exome

AF:

0.901

Gnomad OTH exome

AF:

0.893

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.933

AC:

972484

AN:

1042370

Hom.:

467421

Cov.:

AF XY:

0.934

AC XY:

484419

AN XY:

518604

show subpopulations

Gnomad4 AFR exome

AF:

0.585

Gnomad4 AMR exome

AF:

0.896

Gnomad4 ASJ exome

AF:

0.917

Gnomad4 EAS exome

AF:

0.767

Gnomad4 SAS exome

AF:

0.964

Gnomad4 FIN exome

AF:

0.958

Gnomad4 NFE exome

AF:

0.950

Gnomad4 OTH exome

AF:

0.911

GnomAD4 genome

AF:

0.855

AC:

124800

AN:

145932

Hom.:

54764

Cov.:

AF XY:

0.855

AC XY:

60498

AN XY:

70748

show subpopulations

Gnomad4 AFR

AF:

0.644

Gnomad4 AMR

AF:

0.900

Gnomad4 ASJ

AF:

0.942

Gnomad4 EAS

AF:

0.783

Gnomad4 SAS

AF:

0.964

Gnomad4 FIN

AF:

0.968

Gnomad4 NFE

AF:

0.946

Gnomad4 OTH

AF:

0.858

Alfa

AF:

0.893

Hom.:

10459

Bravo

AF:

0.841

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Feb 17, 2015

- -

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

-0.59

CADD

Benign

DANN

Benign

0.64

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