chr3-170106914-T-G

Variant names:

• chr3-170106914-T-G
• rs1716639290
• NM_024947.4:c.2386A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024947.4(PHC3):​c.2386A>C​(p.Lys796Gln) variant causes a missense change. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K796E) 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: 4.57
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17200336).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHC3	NM_024947.4	c.2386A>C	p.Lys796Gln	missense_variant	Exon 12 of 15	ENST00000495893.7	NP_079223.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHC3	ENST00000495893.7	c.2386A>C	p.Lys796Gln	missense_variant	Exon 12 of 15	1	NM_024947.4	ENSP00000420294.1
PHC3	ENST00000494943.5	c.2350A>C	p.Lys784Gln	missense_variant	Exon 12 of 15	1		ENSP00000420271.1
PHC3	ENST00000467570.5	c.2227A>C	p.Lys743Gln	missense_variant	Exon 11 of 13	2		ENSP00000419089.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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	Benign	0.23
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	.;T;.
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.3	.;L;.
PhyloP100		4.6
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.7	D;D;N
REVEL	Benign	0.081
Sift	Uncertain	0.0060	D;D;D
Sift4G	Uncertain	0.058	T;T;T
Polyphen		0.59	P;P;B
Vest4		0.44
MutPred		0.36		.;Loss of methylation at K784 (P = 0.0013);.;
MVP		0.24
MPC		0.62
ClinPred		0.82	D
GERP RS		6.0
Varity_R		0.20
gMVP		0.42
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1716639290; hg19: chr3-169824702;