rs778867537

Variant names:

• chr6-63684450-C-A
• NM_001370348.2:c.728C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-63684450-C-A
• chr6-63684450-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001370348.2(PHF3):​c.728C>A​(p.Pro243Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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: 6.8e-7 (0 hom.)
• Consequence: PHF3 NM_001370348.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.23

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.017033756).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF3	NM_001370348.2	c.728C>A	p.Pro243Gln	missense_variant	Exon 4 of 16	ENST00000262043.8	NP_001357277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF3	ENST00000262043.8	c.728C>A	p.Pro243Gln	missense_variant	Exon 4 of 16	5	NM_001370348.2	ENSP00000262043.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461586 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727094

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Benign	0.53
DEOGEN2	Benign	0.028	.;T;T;T;.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.51	T;T;T;.;T;T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.017	T;T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-2.2	.;.;.;N;.;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	1.3	N;N;N;N;N;N
REVEL	Benign	0.090
Sift	Benign	1.0	T;T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T
Polyphen		0.0	.;.;.;B;B;B
Vest4		0.16, 0.11, 0.17
MutPred		0.11		.;.;.;Loss of catalytic residue at N241 (P = 0.0715);Loss of catalytic residue at N241 (P = 0.0715);Loss of catalytic residue at N241 (P = 0.0715);
MVP		0.043
MPC		0.069
ClinPred		0.038	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.049
gMVP		0.079

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: chr6-64394351;