6-63680045-G-A

Variant names:

• chr6-63680045-G-A
• rs772580867
• NM_001370348.2:c.290G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001370348.2(PHF3):​c.290G>A​(p.Ser97Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000062 in 1,612,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: PHF3 NM_001370348.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.36
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1649611).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF3	NM_001370348.2	c.290G>A	p.Ser97Asn	missense_variant	Exon 3 of 16	ENST00000262043.8	NP_001357277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF3	ENST00000262043.8	c.290G>A	p.Ser97Asn	missense_variant	Exon 3 of 16	5	NM_001370348.2	ENSP00000262043.4

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152086 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000319 AC: 8 AN: 250722 AF XY: 0.0000295

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000232

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1460500 Hom.: 0 Cov.: 30 AF XY: 0.00000551 AC XY: 4 AN XY: 726572

African (AFR) AF: 0.00 AC: 0 AN: 33424

American (AMR) AF: 0.000201 AC: 9 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26062

East Asian (EAS) AF: 0.00 AC: 0 AN: 39622

South Asian (SAS) AF: 0.00 AC: 0 AN: 86112

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111158

Other (OTH) AF: 0.00 AC: 0 AN: 60322

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152086 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74276

African (AFR) AF: 0.00 AC: 0 AN: 41434

American (AMR) AF: 0.0000655 AC: 1 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67964

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 11, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.290G>A (p.S97N) alteration is located in exon 2 (coding exon 2) of the PHF3 gene. This alteration results from a G to A substitution at nucleotide position 290, causing the serine (S) at amino acid position 97 to be replaced by an asparagine (N). 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	0.32
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.039	T;T;T;.;T;.
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.72	T;T;.;T;T;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.16	T;T;T;T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	0.69	.;.;N;.;N;.
PhyloP100		4.4
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.80	N;N;N;N;N;N
REVEL	Benign	0.12
Sift	Uncertain	0.0020	D;D;D;D;D;D
Sift4G	Uncertain	0.045	D;T;D;T;D;D
Polyphen		1.0, 0.84	.;.;D;P;D;.
Vest4		0.46, 0.49, 0.45
MutPred		0.19		.;.;Loss of glycosylation at S97 (P = 0.0224);Loss of glycosylation at S97 (P = 0.0224);Loss of glycosylation at S97 (P = 0.0224);.;
MVP		0.20
MPC		0.32
ClinPred		0.29	T
GERP RS		5.9
PromoterAI		0.018	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.15
Mutation Taster		=84/16	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: rs772580867; hg19: chr6-64389946;