6-63684515-A-T

Variant names:

• chr6-63684515-A-T
• rs763893625
• NM_001370348.2:c.793A>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.793A>T​(p.Ile265Phe) 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 1,461,088 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: -0.00100

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=0.052100062).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF3	NM_001370348.2	c.793A>T	p.Ile265Phe	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.793A>T	p.Ile265Phe	missense_variant	Exon 4 of 16	5	NM_001370348.2	ENSP00000262043.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250380 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135334

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000329

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461088 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726832

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

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	6.6
DANN	Benign	0.52
DEOGEN2	Benign	0.018	.;T;T;T;.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.71	T;T;T;.;T;T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.052	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	.;.;.;L;.;L
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.49	N;N;N;N;N;N
REVEL	Benign	0.10
Sift	Uncertain	0.018	D;D;D;D;T;D
Sift4G	Uncertain	0.047	D;D;D;T;D;T
Polyphen		0.068, 0.73	.;.;.;B;P;B
Vest4		0.24, 0.22, 0.20
MutPred		0.13		.;.;.;Loss of sheet (P = 0.0357);Loss of sheet (P = 0.0357);Loss of sheet (P = 0.0357);
MVP		0.15
MPC		0.13
ClinPred		0.020	T
GERP RS		-0.74
Varity_R		0.13
gMVP		0.13

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

LitVar

Other links and lift over

dbSNP: rs763893625; hg19: chr6-64394416;