12-8932728-CGCAGCAGCA-CGCA

Position:

• chr12-8932728-CGCAGCAGCA-CGCA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM4 BP6_Moderate BA1

The ENST00000544916.6(PHC1):​c.1284_1289del​(p.Gln438_Gln439del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0185 in 151,848 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (4 hom., cov: 27)
  • Exomes 𝑓: 0.0020 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: PHC1 ENST00000544916.6 inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.09

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 -8 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in ENST00000544916.6.
• BP6: Variant 12-8932728-CGCAGCA-C is Benign according to our data. Variant chr12-8932728-CGCAGCA-C is described in ClinVar as [Benign]. Clinvar id is 376844.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHC1	NM_004426.3	c.1284_1289del	p.Gln438_Gln439del	inframe_deletion	8/15	ENST00000544916.6	NP_004417.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHC1	ENST00000544916.6	c.1284_1289del	p.Gln438_Gln439del	inframe_deletion	8/15	1	NM_004426.3	ENSP00000437659	P1

Frequencies

GnomAD3 genomes AF: 0.0185 AC: 2812 AN: 151732 Hom.: 4 Cov.: 27

Gnomad AFR AF: 0.0622

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0142

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0120

GnomAD3 exomes AF: 0.00385 AC: 955 AN: 248330 Hom.: 0 AF XY: 0.00285 AC XY: 383 AN XY: 134438

Gnomad AFR exome AF: 0.0498

Gnomad AMR exome AF: 0.00454

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000240

Gnomad OTH exome AF: 0.00164

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00197 AC: 2880 AN: 1460808 Hom.: 1 AF XY: 0.00170 AC XY: 1236 AN XY: 726696

Gnomad4 AFR exome AF: 0.0619

Gnomad4 AMR exome AF: 0.00671

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000186

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000224

Gnomad4 OTH exome AF: 0.00396

GnomAD4 genome AF: 0.0185 AC: 2815 AN: 151848 Hom.: 4 Cov.: 27 AF XY: 0.0178 AC XY: 1324 AN XY: 74230

Gnomad4 AFR AF: 0.0621

Gnomad4 AMR AF: 0.0141

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.0118

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Jan 09, 2017

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs368945524; hg19: chr12-9085324;