chr6-63646702-G-C

Variant names:

• chr6-63646702-G-C
• rs1764797672
• NM_001370348.2:c.151G>C

Variant summary

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

The NM_001370348.2(PHF3):​c.151G>C​(p.Asp51His) variant causes a missense change involving the alteration of a 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. D51N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PHF3 NM_001370348.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.28
• Publications: 0 publications found

Genes affected

PHF3 (HGNC:8921): (PHD finger protein 3) This gene encodes a member of a PHD finger-containing gene family. This gene may function as a transcription factor and may be involved in glioblastomas development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

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
PHF3	NM_001370348.2	c.151G>C	p.Asp51His	missense_variant	Exon 2 of 16	ENST00000262043.8	NP_001357277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF3	ENST00000262043.8	c.151G>C	p.Asp51His	missense_variant	Exon 2 of 16	5	NM_001370348.2	ENSP00000262043.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	30
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T;T;.;T
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.89
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;.;D;D
M_CAP	Benign	0.077	D
MetaRNN	Uncertain	0.59	D;D;D;D
MetaSVM	Uncertain	0.020	D
MutationAssessor	Benign	0.97	.;L;.;L
PhyloP100		9.3
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-3.1	D;N;D;N
REVEL	Uncertain	0.48
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	.;D;D;D
Vest4		0.83, 0.88, 0.85
MutPred		0.17		.;Loss of solvent accessibility (P = 0.0442);Loss of solvent accessibility (P = 0.0442);Loss of solvent accessibility (P = 0.0442);
MVP		0.73
MPC		0.47
ClinPred		0.91	D
GERP RS		5.7
PromoterAI		-0.042	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.36
gMVP		0.57
Mutation Taster		=25/75	disease causing

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: rs1764797672; hg19: chr6-64356607;