chr3-170102573-T-C

Variant names:

• chr3-170102573-T-C
• rs766508751
• NM_024947.4:c.2739A>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Moderate BP7 BS2

The NM_024947.4(PHC3):​c.2739A>G​(p.Lys913Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,616 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: PHC3 NM_024947.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205
• 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.129).
• BP7: Synonymous conserved (PhyloP=-0.205 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHC3	NM_024947.4	c.2739A>G	p.Lys913Lys	synonymous_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.2739A>G	p.Lys913Lys	synonymous_variant	Exon 14 of 15	1	NM_024947.4	ENSP00000420294.1
PHC3	ENST00000494943.5	c.2703A>G	p.Lys901Lys	synonymous_variant	Exon 14 of 15	1		ENSP00000420271.1
PHC3	ENST00000484068.5	c.234A>G	p.Lys78Lys	synonymous_variant	Exon 2 of 4	4		ENSP00000418835.1
PHC3	ENST00000467570.5	c.*68A>G		3_prime_UTR_variant	Exon 13 of 13	2		ENSP00000419089.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461616 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727096

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39690

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111822

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	5.3
DANN	Benign	0.49
PhyloP100		-0.20
PromoterAI		0.0062	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: rs766508751; hg19: chr3-169820361;