6-63684440-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001370348.2(PHF3):c.718T>C(p.Cys240Arg) variant causes a missense 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PHF3 NM_001370348.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.766

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.080280334).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHF3	NM_001370348.2	c.718T>C	p.Cys240Arg	missense_variant	4/16	ENST00000262043.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHF3	ENST00000262043.8	c.718T>C	p.Cys240Arg	missense_variant	4/16	5	NM_001370348.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 28, 2023

The c.718T>C (p.C240R) alteration is located in exon 3 (coding exon 3) of the PHF3 gene. This alteration results from a T to C substitution at nucleotide position 718, causing the cysteine (C) at amino acid position 240 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
Cadd	Benign	18
Dann	Benign	0.82
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.71	T;T;T;.;T;T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.080	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.9	N;N;N;N;D;N
REVEL	Benign	0.096
Sift	Benign	0.098	T;T;T;D;T;D
Sift4G	Benign	0.13	T;T;T;D;T;D
Polyphen		0.0010, 0.063	.;.;.;B;B;B
Vest4		0.48, 0.30, 0.30
MutPred		0.28		.;.;.;Gain of solvent accessibility (P = 0.026);Gain of solvent accessibility (P = 0.026);Gain of solvent accessibility (P = 0.026);
MVP		0.13
MPC		0.14
ClinPred		0.32	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.29
gMVP		0.18

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-64394341;