NM_001370348.2:c.737T>C

Variant names:

• chr6-63684459-T-C
• rs181643726
• NM_001370348.2:c.737T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001370348.2(PHF3):​c.737T>C​(p.Ile246Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000049 in 1,613,724 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000048 (1 hom.)
• Consequence: PHF3 NM_001370348.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.389
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011719316).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370348.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF3	NM_001370348.2	MANE Select	c.737T>C	p.Ile246Thr	missense	Exon 4 of 16	NP_001357277.1	Q92576-1
	PHF3	NM_015153.4		c.737T>C	p.Ile246Thr	missense	Exon 3 of 15	NP_055968.1	Q92576-1
	PHF3	NM_001290259.2		c.473T>C	p.Ile158Thr	missense	Exon 5 of 17	NP_001277188.1	Q92576-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF3	ENST00000262043.8	TSL:5 MANE Select	c.737T>C	p.Ile246Thr	missense	Exon 4 of 16	ENSP00000262043.4	Q92576-1
	PHF3	ENST00000393387.5	TSL:1	c.737T>C	p.Ile246Thr	missense	Exon 3 of 15	ENSP00000377048.1	Q92576-1
	PHF3	ENST00000506783.5	TSL:1	c.179T>C	p.Ile60Thr	missense	Exon 2 of 12	ENSP00000424694.1	E7EVH3

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152170 Hom.: 0 Cov.: 32

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: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000677 AC: 17 AN: 251156 AF XY: 0.0000663

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000114

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000479 AC: 70 AN: 1461436 Hom.: 1 Cov.: 32 AF XY: 0.0000426 AC XY: 31 AN XY: 727056

African (AFR) AF: 0.0000299 AC: 1 AN: 33470

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53402

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.0000540 AC: 60 AN: 1111652

Other (OTH) AF: 0.0000497 AC: 3 AN: 60380

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152288 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74480

African (AFR) AF: 0.00 AC: 0 AN: 41554

American (AMR) AF: 0.0000654 AC: 1 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000107 Hom.: 0

Bravo AF: 0.0000567

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000576 AC: 7

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	11
DANN	Benign	0.34
DEOGEN2	Benign	0.0048	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.1	N
PhyloP100		0.39
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.014
Sift	Benign	0.42	T
Sift4G	Benign	0.33	T
Polyphen		0.0	B
Vest4		0.066
MVP		0.11
MPC		0.094
ClinPred		0.011	T
GERP RS		0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.058
gMVP		0.053
Mutation Taster		=98/2	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: rs181643726; hg19: chr6-64394360;