chr3-170102851-C-A

Variant names:

• chr3-170102851-C-A
• rs778400657
• NM_024947.4:c.2552G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024947.4(PHC3):​c.2552G>T​(p.Arg851Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R851H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PHC3 NM_024947.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.85
• Publications: 2 publications found

Genes affected

PHC3 (HGNC:15682): (polyhomeotic homolog 3) Predicted to enable chromatin binding activity and histone binding activity. Predicted to be involved in negative regulation of transcription, DNA-templated. Located in nucleoplasm. Part of PRC1 complex. [provided by Alliance of Genome Resources, Apr 2022]

LOC105374209 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHC3	NM_024947.4	c.2552G>T	p.Arg851Leu	missense_variant	Exon 13 of 15	ENST00000495893.7	NP_079223.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHC3	ENST00000495893.7	c.2552G>T	p.Arg851Leu	missense_variant	Exon 13 of 15	1	NM_024947.4	ENSP00000420294.1
PHC3	ENST00000494943.5	c.2516G>T	p.Arg839Leu	missense_variant	Exon 13 of 15	1		ENSP00000420271.1
PHC3	ENST00000467570.5	c.2393G>T	p.Arg798Leu	missense_variant	Exon 12 of 13	2		ENSP00000419089.1
PHC3	ENST00000484068.5	c.47G>T	p.Arg16Leu	missense_variant	Exon 1 of 4	4		ENSP00000418835.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 248644 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	.;T;.
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.61	D;D;D
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.0	.;M;.
PhyloP100		5.8
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.9	D;D;D
REVEL	Benign	0.20
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.022	D;D;T
Polyphen		0.97	D;D;D
Vest4		0.66
MutPred		0.30		.;Loss of methylation at R839 (P = 0.0139);.;
MVP		0.33
MPC		0.65
ClinPred		0.97	D
GERP RS		5.5
PromoterAI		0.026	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.38
gMVP		0.61
Mutation Taster		=70/30	polymorphism

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

Other links and lift over

dbSNP: rs778400657; hg19: chr3-169820639;