chr3-170102907-A-G

Variant names:

• chr3-170102907-A-G
• rs759442387
• NM_024947.4:c.2496T>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_024947.4(PHC3):​c.2496T>C​(p.Phe832Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PHC3 NM_024947.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.86
• 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]

LOC105374209 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP7: Synonymous conserved (PhyloP=2.86 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHC3	NM_024947.4	c.2496T>C	p.Phe832Phe	synonymous_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.2496T>C	p.Phe832Phe	synonymous_variant	Exon 13 of 15	1	NM_024947.4	ENSP00000420294.1
PHC3	ENST00000494943.5	c.2460T>C	p.Phe820Phe	synonymous_variant	Exon 13 of 15	1		ENSP00000420271.1
PHC3	ENST00000467570.5	c.2337T>C	p.Phe779Phe	synonymous_variant	Exon 12 of 13	2		ENSP00000419089.1
PHC3	ENST00000484068.5	c.-10T>C		upstream_gene_variant		4		ENSP00000418835.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	13
DANN	Benign	0.63
PhyloP100		2.9
PromoterAI		0.0071	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs759442387; hg19: chr3-169820695;