rs1805777

chr12-8930740-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 3.08

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]

ACMG classification

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	UniProt
PHC1	NM_004426.3	c.918A>G	p.Arg306=	synonymous_variant	7/15	ENST00000544916.6

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.855 AC: 124731 AN: 145816 Hom.: 54741 Cov.: 20

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

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.: 16 AF XY: 0.934 AC XY: 484419 AN XY: 518604

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.: 20 AF XY: 0.855 AC XY: 60498 AN XY: 70748

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 09, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	10
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

Other links and lift over

dbSNP: rs1805777; hg19: chr12-9083336; COSMIC: COSV70418015; COSMIC: COSV70418015;