6-63646806-CTTTTTTTTTTTTTT-CTTTTTTTTTTTT

Variant names:

• chr6-63646806-CTT-C
• rs11285703
• NM_001370348.2:c.244+32_244+33delTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001370348.2(PHF3):​c.244+32_244+33delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 979,352 control chromosomes in the GnomAD database, including 85 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.027 (76 hom., cov: 0)
  • Exomes 𝑓: 0.15 (9 hom.)
• Consequence: PHF3 NM_001370348.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• Publications: 1 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0865 is higher than 0.05.

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.244+32_244+33delTT		intron	N/A	NP_001357277.1	Q92576-1
	PHF3	NM_015153.4		c.244+32_244+33delTT		intron	N/A	NP_055968.1	Q92576-1
	PHF3	NM_001290259.2		c.-214+32_-214+33delTT		intron	N/A	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.244+12_244+13delTT		intron	N/A	ENSP00000262043.4	Q92576-1
	PHF3	ENST00000393387.5	TSL:1	c.244+12_244+13delTT		intron	N/A	ENSP00000377048.1	Q92576-1
	PHF3	ENST00000506783.5	TSL:1	c.-153+10657_-153+10658delTT		intron	N/A	ENSP00000424694.1	E7EVH3

Frequencies

GnomAD3 genomes AF: 0.0265 AC: 2254 AN: 85114 Hom.: 76 Cov.: 0

Gnomad AFR AF: 0.0899

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0159

Gnomad ASJ AF: 0.00758

Gnomad EAS AF: 0.00101

Gnomad SAS AF: 0.000864

Gnomad FIN AF: 0.00146

Gnomad MID AF: 0.0234

Gnomad NFE AF: 0.00339

Gnomad OTH AF: 0.0164

GnomAD2 exomes AF: 0.00219 AC: 57 AN: 26084 AF XY: 0.00103

Gnomad AFR exome AF: 0.00162

Gnomad AMR exome AF: 0.000740

Gnomad ASJ exome AF: 0.0107

Gnomad EAS exome AF: 0.00108

Gnomad FIN exome AF: 0.00323

Gnomad NFE exome AF: 0.00206

Gnomad OTH exome AF: 0.00622

GnomAD4 exome AF: 0.152 AC: 135576 AN: 894256 Hom.: 9 AF XY: 0.151 AC XY: 64309 AN XY: 426156

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

African (AFR) AF: 0.221 AC: 4132 AN: 18712

American (AMR) AF: 0.142 AC: 1370 AN: 9638

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 2017 AN: 11648

East Asian (EAS) AF: 0.172 AC: 3803 AN: 22156

South Asian (SAS) AF: 0.150 AC: 2693 AN: 17912

European-Finnish (FIN) AF: 0.158 AC: 2953 AN: 18638

Middle Eastern (MID) AF: 0.172 AC: 405 AN: 2358

European-Non Finnish (NFE) AF: 0.148 AC: 112419 AN: 757688

Other (OTH) AF: 0.163 AC: 5784 AN: 35506

⚠️ 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 AF: 0.0265 AC: 2256 AN: 85096 Hom.: 76 Cov.: 0 AF XY: 0.0267 AC XY: 1048 AN XY: 39184

African (AFR) AF: 0.0899 AC: 1933 AN: 21510

American (AMR) AF: 0.0159 AC: 128 AN: 8058

Ashkenazi Jewish (ASJ) AF: 0.00758 AC: 18 AN: 2376

East Asian (EAS) AF: 0.00101 AC: 3 AN: 2964

South Asian (SAS) AF: 0.000870 AC: 2 AN: 2300

European-Finnish (FIN) AF: 0.00146 AC: 4 AN: 2732

Middle Eastern (MID) AF: 0.0254 AC: 3 AN: 118

European-Non Finnish (NFE) AF: 0.00340 AC: 147 AN: 43292

Other (OTH) AF: 0.0163 AC: 18 AN: 1106

Alfa AF: 0.000689 Hom.: 238

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3
Mutation Taster		=99/1	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: rs11285703; hg19: chr6-64356711;