Genetic Variant PHF3:c.244+26_244+33delTTTTTTTT (chr6-63646806-CTTTTTTTT-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001370348.2(PHF3):c.244+26_244+33delTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000178 in 1,013,484 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000035 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

PHF3
NM_001370348.2 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.50

Publications

1 publications found

Variant links:

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]

PHF3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PHF3	NM_001370348.2	MANE Select	c.244+26_244+33delTTTTTTTT	intron	N/A	NP_001357277.1	Q92576-1
PHF3	NM_015153.4		c.244+26_244+33delTTTTTTTT	intron	N/A	NP_055968.1	Q92576-1
PHF3	NM_001290259.2		c.-214+26_-214+33delTTTTTTTT	intron	N/A	NP_001277188.1	Q92576-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PHF3	ENST00000262043.8	TSL:5 MANE Select	c.244+12_244+19delTTTTTTTT	intron	N/A	ENSP00000262043.4	Q92576-1
PHF3	ENST00000393387.5	TSL:1	c.244+12_244+19delTTTTTTTT	intron	N/A	ENSP00000377048.1	Q92576-1
PHF3	ENST00000506783.5	TSL:1	c.-153+10657_-153+10664delTTTTTTTT	intron	N/A	ENSP00000424694.1	E7EVH3

Frequencies

GnomAD3 genomes

AF:

0.0000353

AC:

AN:

85068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000336

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000462

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000162

AC:

AN:

928434

Hom.:

AF XY:

0.0000113

AC XY:

AN XY:

442344

show subpopulations

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

African (AFR)

AF:

0.0000519

AC:

AN:

19270

American (AMR)

AF:

0.00

AC:

AN:

9848

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12028

East Asian (EAS)

AF:

0.0000435

AC:

AN:

22996

South Asian (SAS)

AF:

0.0000539

AC:

AN:

18568

European-Finnish (FIN)

AF:

0.00

AC:

AN:

19366

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2434

European-Non Finnish (NFE)

AF:

0.0000127

AC:

AN:

787108

Other (OTH)

AF:

0.0000543

AC:

AN:

36816

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000000000417444), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.308

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000353

AC:

AN:

85050

Hom.:

Cov.:

AF XY:

0.0000511

AC XY:

AN XY:

39154

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

21462

American (AMR)

AF:

0.00

AC:

AN:

8056

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2376

East Asian (EAS)

AF:

0.000337

AC:

AN:

2964

South Asian (SAS)

AF:

0.00

AC:

AN:

2302

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2732

Middle Eastern (MID)

AF:

0.00

AC:

AN:

118

European-Non Finnish (NFE)

AF:

0.0000462

AC:

AN:

43294

Other (OTH)

AF:

0.00

AC:

AN:

1106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.725

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

238

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over