6-63684375-G-A

Variant names:

• chr6-63684375-G-A
• rs1766578326
• NM_001370348.2:c.653G>A

Variant summary

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

The NM_001370348.2(PHF3):​c.653G>A​(p.Ser218Asn) 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 1,461,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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. S218T) has been classified as Uncertain significance.

• 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: 2.25
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08901).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF3	NM_001370348.2	c.653G>A	p.Ser218Asn	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.653G>A	p.Ser218Asn	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: 1461672 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727136

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111836

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	16
DANN	Benign	0.78
DEOGEN2	Benign	0.018	.;T;T;T;.;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.66	T;T;T;.;T;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.089	T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	.;.;.;L;.;L
PhyloP100		2.2
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.55	N;N;N;N;N;N
REVEL	Benign	0.044
Sift	Uncertain	0.0080	D;D;D;D;T;D
Sift4G	Benign	0.24	T;T;T;T;T;T
Polyphen		0.18, 0.40	.;.;.;B;B;B
Vest4		0.27, 0.16, 0.20
MutPred		0.15		.;.;.;Loss of phosphorylation at S218 (P = 0.0061);Loss of phosphorylation at S218 (P = 0.0061);Loss of phosphorylation at S218 (P = 0.0061);
MVP		0.15
MPC		0.099
ClinPred		0.12	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.090
gMVP		0.095
Mutation Taster		=93/7	polymorphism

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: rs1766578326; hg19: chr6-64394276;