3-170102601-C-G

Variant names:

• chr3-170102601-C-G
• rs758338434
• NM_024947.4:c.2711G>C

Variant summary

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

The NM_024947.4(PHC3):​c.2711G>C​(p.Arg904Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. R904H) 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: 3.00
• Publications: 0 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]

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.2711G>C	p.Arg904Pro	missense_variant	Exon 14 of 15	ENST00000495893.7	NP_079223.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHC3	ENST00000495893.7	c.2711G>C	p.Arg904Pro	missense_variant	Exon 14 of 15	1	NM_024947.4	ENSP00000420294.1
PHC3	ENST00000494943.5	c.2675G>C	p.Arg892Pro	missense_variant	Exon 14 of 15	1		ENSP00000420271.1
PHC3	ENST00000484068.5	c.206G>C	p.Arg69Pro	missense_variant	Exon 2 of 4	4		ENSP00000418835.1
PHC3	ENST00000467570.5	c.*40G>C		3_prime_UTR_variant	Exon 13 of 13	2		ENSP00000419089.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Uncertain	0.035	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	.;T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	1.6	.;L
PhyloP100		3.0
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.17
Sift	Benign	0.064	T;T
Sift4G	Benign	0.13	T;T
Polyphen		0.98	D;D
Vest4		0.52
MutPred		0.39		.;Loss of MoRF binding (P = 0.0045);
MVP		0.23
MPC		0.24
ClinPred		0.88	D
GERP RS		5.1
PromoterAI		-0.050	Neutral
Varity_R		0.59
gMVP		0.55
Mutation Taster		=73/27	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: rs758338434; hg19: chr3-169820389;