chr6-63646806-C-CT

Variant names:

• chr6-63646806-C-CT
• rs11285703
• NM_001370348.2:c.244+33dupT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001370348.2(PHF3):​c.244+33dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.011 (12 hom., cov: 0)
  • Exomes 𝑓: 0.032 (0 hom.)
• Consequence: PHF3 NM_001370348.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• 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.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0111 (942/85034) while in subpopulation AFR AF = 0.0301 (646/21458). AF 95% confidence interval is 0.0282. There are 12 homozygotes in GnomAd4. There are 404 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 gene

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+33dupT		intron	N/A	NP_001357277.1	Q92576-1
	PHF3	NM_015153.4		c.244+33dupT		intron	N/A	NP_055968.1	Q92576-1
	PHF3	NM_001290259.2		c.-214+33dupT		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+11_244+12insT		intron	N/A	ENSP00000262043.4	Q92576-1
	PHF3	ENST00000393387.5	TSL:1	c.244+11_244+12insT		intron	N/A	ENSP00000377048.1	Q92576-1
	PHF3	ENST00000506783.5	TSL:1	c.-153+10656_-153+10657insT		intron	N/A	ENSP00000424694.1	E7EVH3

Frequencies

GnomAD3 genomes AF: 0.0111 AC: 941 AN: 85052 Hom.: 12 Cov.: 0

Gnomad AFR AF: 0.0301

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00435

Gnomad ASJ AF: 0.000421

Gnomad EAS AF: 0.00773

Gnomad SAS AF: 0.00561

Gnomad FIN AF: 0.00220

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00469

Gnomad OTH AF: 0.0137

GnomAD2 exomes AF: 0.000153 AC: 4 AN: 26084 AF XY: 0.000138

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00215

Gnomad EAS exome AF: 0.000538

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000133

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0322 AC: 29587 AN: 918932 Hom.: 0 Cov.: 0 AF XY: 0.0318 AC XY: 13915 AN XY: 437890

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

African (AFR) AF: 0.0279 AC: 533 AN: 19102

American (AMR) AF: 0.0115 AC: 113 AN: 9790

Ashkenazi Jewish (ASJ) AF: 0.0254 AC: 303 AN: 11940

East Asian (EAS) AF: 0.0278 AC: 635 AN: 22820

South Asian (SAS) AF: 0.0270 AC: 496 AN: 18396

European-Finnish (FIN) AF: 0.0227 AC: 437 AN: 19268

Middle Eastern (MID) AF: 0.0325 AC: 78 AN: 2398

European-Non Finnish (NFE) AF: 0.0333 AC: 25932 AN: 778792

Other (OTH) AF: 0.0291 AC: 1060 AN: 36426

⚠️ 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: 0.0111 AC: 942 AN: 85034 Hom.: 12 Cov.: 0 AF XY: 0.0103 AC XY: 404 AN XY: 39144

African (AFR) AF: 0.0301 AC: 646 AN: 21458

American (AMR) AF: 0.00435 AC: 35 AN: 8052

Ashkenazi Jewish (ASJ) AF: 0.000421 AC: 1 AN: 2376

East Asian (EAS) AF: 0.00776 AC: 23 AN: 2964

South Asian (SAS) AF: 0.00565 AC: 13 AN: 2302

European-Finnish (FIN) AF: 0.00220 AC: 6 AN: 2732

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 118

European-Non Finnish (NFE) AF: 0.00469 AC: 203 AN: 43286

Other (OTH) AF: 0.0136 AC: 15 AN: 1106

Alfa AF: 0.00 Hom.: 238

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
Mutation Taster		=100/0	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;