6-63646733-A-C

Variant names:

• chr6-63646733-A-C
• NM_001370348.2:c.182A>C

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.182A>C​(p.Asn61Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N61D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PHF3 NM_001370348.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.91
• 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=0.09377313).

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.182A>C	p.Asn61Thr	missense	Exon 2 of 16	NP_001357277.1	Q92576-1
	PHF3	NM_015153.4		c.182A>C	p.Asn61Thr	missense	Exon 1 of 15	NP_055968.1	Q92576-1
	PHF3	NM_001290260.2		c.182A>C	p.Asn61Thr	missense	Exon 2 of 4	NP_001277189.1	D6R9X2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF3	ENST00000262043.8	TSL:5 MANE Select	c.182A>C	p.Asn61Thr	missense	Exon 2 of 16	ENSP00000262043.4	Q92576-1
	PHF3	ENST00000393387.5	TSL:1	c.182A>C	p.Asn61Thr	missense	Exon 1 of 15	ENSP00000377048.1	Q92576-1
	PHF3	ENST00000509330.5	TSL:1	c.182A>C	p.Asn61Thr	missense	Exon 2 of 4	ENSP00000422841.1	D6R9X2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460128 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726456

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33394

American (AMR) AF: 0.00 AC: 0 AN: 44368

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26078

East Asian (EAS) AF: 0.00 AC: 0 AN: 39546

South Asian (SAS) AF: 0.00 AC: 0 AN: 86088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111270

Other (OTH) AF: 0.00 AC: 0 AN: 60298

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

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	0.18
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	23
DANN	Benign	0.93
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.057
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		4.9
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.94	N
REVEL	Benign	0.059
Sift	Benign	0.15	T
Sift4G	Benign	1.0	T
Polyphen		0.042	B
Vest4		0.46
MVP		0.12
MPC		0.080
ClinPred		0.32	T
GERP RS		5.7
PromoterAI		-0.012	Neutral
Varity_R		0.10
gMVP		0.059
Mutation Taster		=76/24	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

hg19: chr6-64356638;