Variant chr12-8917770-T-A 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.93T>A(p.Leu31Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 1,561,100 control chromosomes in the GnomAD database, including 401,041 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 34995 hom., cov: 30)

Exomes 𝑓: 0.72 ( 366046 hom. )

Consequence

PHC1
NM_004426.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0380

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=-0.5).

BP6

Variant 12-8917770-T-A is Benign according to our data. Variant chr12-8917770-T-A is described in ClinVar as [Benign]. Clinvar id is 1271948.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.038 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHC1	NM_004426.3 link	c.93T>A	p.Leu31Leu	synonymous_variant	2/15	ENST00000544916.6	NP_004417.2	P78364Q6GMQ3Q6N083

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHC1	ENST00000544916.6 link	c.93T>A	p.Leu31Leu	synonymous_variant	2/15	1	NM_004426.3	ENSP00000437659.1		P78364

Frequencies

GnomAD3 genomes

AF:

0.675

AC:

102498

AN:

151758

Hom.:

34987

Cov.:

show subpopulations

Gnomad AFR

AF:

0.589

Gnomad AMI

AF:

0.637

Gnomad AMR

AF:

0.625

Gnomad ASJ

AF:

0.804

Gnomad EAS

AF:

0.752

Gnomad SAS

AF:

0.833

Gnomad FIN

AF:

0.685

Gnomad MID

AF:

0.788

Gnomad NFE

AF:

0.714

Gnomad OTH

AF:

0.687

GnomAD3 exomes

AF:

0.709

AC:

157941

AN:

222630

Hom.:

56551

AF XY:

0.721

AC XY:

87489

AN XY:

121278

show subpopulations

Gnomad AFR exome

AF:

0.578

Gnomad AMR exome

AF:

0.618

Gnomad ASJ exome

AF:

0.800

Gnomad EAS exome

AF:

0.743

Gnomad SAS exome

AF:

0.826

Gnomad FIN exome

AF:

0.688

Gnomad NFE exome

AF:

0.712

Gnomad OTH exome

AF:

0.730

GnomAD4 exome

AF:

0.719

AC:

1012923

AN:

1409224

Hom.:

366046

Cov.:

AF XY:

0.723

AC XY:

507856

AN XY:

702106

show subpopulations

Gnomad4 AFR exome

AF:

0.583

Gnomad4 AMR exome

AF:

0.621

Gnomad4 ASJ exome

AF:

0.800

Gnomad4 EAS exome

AF:

0.745

Gnomad4 SAS exome

AF:

0.829

Gnomad4 FIN exome

AF:

0.683

Gnomad4 NFE exome

AF:

0.716

Gnomad4 OTH exome

AF:

0.724

GnomAD4 genome

AF:

0.675

AC:

102545

AN:

151876

Hom.:

34995

Cov.:

AF XY:

0.674

AC XY:

49997

AN XY:

74222

show subpopulations

Gnomad4 AFR

AF:

0.589

Gnomad4 AMR

AF:

0.625

Gnomad4 ASJ

AF:

0.804

Gnomad4 EAS

AF:

0.753

Gnomad4 SAS

AF:

0.832

Gnomad4 FIN

AF:

0.685

Gnomad4 NFE

AF:

0.714

Gnomad4 OTH

AF:

0.686

Alfa

AF:

0.694

Hom.:

9677

Bravo

AF:

0.665

Asia WGS

AF:

0.763

AC:

2652

AN:

3478

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

-0.50

CADD

Benign

4.4

DANN

Benign

0.68

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