rs202158376

Positions:

• chr12-8932993-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP6_Very_Strong BP7

The NM_004426.3(PHC1):​c.1536C>T​(p.Ala512Ala) 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 Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0093 (2 hom., cov: 20)
  • Exomes 𝑓: 0.0014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PHC1 NM_004426.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.388

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 12-8932993-C-T is Benign according to our data. Variant chr12-8932993-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 436307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-8932993-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.388 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHC1	NM_004426.3	c.1536C>T	p.Ala512Ala	synonymous_variant	8/15	ENST00000544916.6	NP_004417.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHC1	ENST00000544916.6	c.1536C>T	p.Ala512Ala	synonymous_variant	8/15	1	NM_004426.3	ENSP00000437659.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1210 AN: 130674 Hom.: 2 Cov.: 20 FAILED QC

Gnomad AFR AF: 0.0327

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00452

Gnomad ASJ AF: 0.000309

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000273

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00340

Gnomad NFE AF: 0.000227

Gnomad OTH AF: 0.0130

GnomAD3 exomes AF: 0.00282 AC: 223 AN: 79076 Hom.: 1 AF XY: 0.00222 AC XY: 89 AN XY: 40082

Gnomad AFR exome AF: 0.0318

Gnomad AMR exome AF: 0.00159

Gnomad ASJ exome AF: 0.000348

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000105

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000212

Gnomad OTH exome AF: 0.000401

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00138 AC: 771 AN: 558116 Hom.: 0 Cov.: 6 AF XY: 0.00114 AC XY: 334 AN XY: 291880

Gnomad4 AFR exome AF: 0.0341

Gnomad4 AMR exome AF: 0.00186

Gnomad4 ASJ exome AF: 0.000608

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000745

Gnomad4 FIN exome AF: 0.0000274

Gnomad4 NFE exome AF: 0.000188

Gnomad4 OTH exome AF: 0.00318

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00928 AC: 1214 AN: 130762 Hom.: 2 Cov.: 20 AF XY: 0.00906 AC XY: 560 AN XY: 61844

Gnomad4 AFR AF: 0.0327

Gnomad4 AMR AF: 0.00451

Gnomad4 ASJ AF: 0.000309

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000273

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000227

Gnomad4 OTH AF: 0.0129

Alfa AF: 0.00600 Hom.: 1

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

May 24, 2017

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	8.9
DANN	Benign	0.48

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: rs202158376; hg19: chr12-9085589;