Menu
GeneBe

rs140650800

chr12-8919803-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_004426.3(PHC1):c.162C>T(p.His54=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00075 in 1,612,592 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00077 ( 1 hom. )

Consequence

PHC1
NM_004426.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.64
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-8919803-C-T is Benign according to our data. Variant chr12-8919803-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 436300.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=2.64 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PHC1NM_004426.3 linkuse as main transcriptc.162C>T p.His54= synonymous_variant 3/15 ENST00000544916.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PHC1ENST00000544916.6 linkuse as main transcriptc.162C>T p.His54= synonymous_variant 3/151 NM_004426.3 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000532
AC:
81
AN:
152216
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000851
Gnomad ASJ
AF:
0.000576
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000823
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000602
AC:
150
AN:
249286
Hom.:
0
AF XY:
0.000638
AC XY:
86
AN XY:
134702
show subpopulations
Gnomad AFR exome
AF:
0.0000635
Gnomad AMR exome
AF:
0.000233
Gnomad ASJ exome
AF:
0.000601
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000463
Gnomad FIN exome
AF:
0.0000464
Gnomad NFE exome
AF:
0.00104
Gnomad OTH exome
AF:
0.000492
GnomAD4 exome
AF:
0.000773
AC:
1129
AN:
1460258
Hom.:
1
Cov.:
31
AF XY:
0.000775
AC XY:
563
AN XY:
726316
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000292
Gnomad4 ASJ exome
AF:
0.000345
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000361
Gnomad4 FIN exome
AF:
0.000131
Gnomad4 NFE exome
AF:
0.000919
Gnomad4 OTH exome
AF:
0.000779
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000532
AC:
81
AN:
152334
Hom.:
0
Cov.:
32
AF XY:
0.000470
AC XY:
35
AN XY:
74488
show subpopulations
Gnomad4 AFR
AF:
0.000241
Gnomad4 AMR
AF:
0.000850
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000823
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000960
Hom.:
0
Bravo
AF:
0.000582
EpiCase
AF:
0.000818
EpiControl
AF:
0.000830

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoFeb 20, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.33
Cadd
Benign
13
Dann
Benign
0.71

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.

Other links and lift over

dbSNP: rs140650800; hg19: chr12-9072399; API