12-8930738-AGA-CGG

Variant names:

• chr12-8930738-AGA-CGG
• NM_004426.3:c.916_918delAGAinsCGG
• PHC1 p.307

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_004426.3(PHC1):​c.916_918delAGAinsCGG​(p.307) variant causes a synonymous change. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R306R) has been classified as Benign.

• Frequency: Genomes: not found (cov: 20)
• Consequence: PHC1 NM_004426.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.83
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• autosomal recessive primary microcephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• microcephaly 11, primary, autosomal recessive

  Inheritance: AR Classification: LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004426.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHC1	NM_004426.3	MANE Select	c.916_918delAGAinsCGG	p.307	synonymous	N/A	NP_004417.2	P78364
	PHC1	NM_001413738.1		c.916_918delAGAinsCGG	p.307	synonymous	N/A	NP_001400667.1	P78364
	PHC1	NM_001413739.1		c.910_912delAGAinsCGG	p.305	synonymous	N/A	NP_001400668.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHC1	ENST00000544916.6	TSL:1 MANE Select	c.916_918delAGAinsCGG	p.307	synonymous	N/A	ENSP00000437659.1	P78364
	PHC1	ENST00000543824.5	TSL:1	c.916_918delAGAinsCGG	p.307	synonymous	N/A	ENSP00000440674.1	P78364
	PHC1	ENST00000433083.6	TSL:1	c.781_783delAGAinsCGG	p.262	synonymous	N/A	ENSP00000399194.2	J3KQH6

Frequencies

GnomAD3 genomes Cov.: 20

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 20

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.8

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-9083334;