NM_001370348.2:c.244+30_244+33delTTTT

Variant names:

• chr6-63646806-CTTTT-C
• rs11285703
• NM_001370348.2:c.244+30_244+33delTTTT

Variant summary

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

The NM_001370348.2(PHF3):​c.244+30_244+33delTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00691 in 1,002,502 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: 0.0075 (0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Variant has high frequency in the AFR (0.0127) population. However there is too low homozygotes in high coverage region: (expected more than 11, got 0).

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+30_244+33delTTTT		intron	N/A	NP_001357277.1	Q92576-1
	PHF3	NM_015153.4		c.244+30_244+33delTTTT		intron	N/A	NP_055968.1	Q92576-1
	PHF3	NM_001290259.2		c.-214+30_-214+33delTTTT		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+15delTTTT		intron	N/A	ENSP00000262043.4	Q92576-1
	PHF3	ENST00000393387.5	TSL:1	c.244+12_244+15delTTTT		intron	N/A	ENSP00000377048.1	Q92576-1
	PHF3	ENST00000506783.5	TSL:1	c.-153+10657_-153+10660delTTTT		intron	N/A	ENSP00000424694.1	E7EVH3

Frequencies

GnomAD3 genomes AF: 0.0000353 AC: 3 AN: 85068 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000466

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000462

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000307 AC: 8 AN: 26084 AF XY: 0.00

Gnomad AFR exome AF: 0.000405

Gnomad AMR exome AF: 0.000370

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000399

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00754 AC: 6920 AN: 917434 Hom.: 0 AF XY: 0.00766 AC XY: 3347 AN XY: 436840

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

African (AFR) AF: 0.0141 AC: 267 AN: 18958

American (AMR) AF: 0.0134 AC: 130 AN: 9678

Ashkenazi Jewish (ASJ) AF: 0.0114 AC: 135 AN: 11824

East Asian (EAS) AF: 0.0114 AC: 257 AN: 22512

South Asian (SAS) AF: 0.00718 AC: 132 AN: 18380

European-Finnish (FIN) AF: 0.0126 AC: 239 AN: 19004

Middle Eastern (MID) AF: 0.00958 AC: 23 AN: 2402

European-Non Finnish (NFE) AF: 0.00692 AC: 5389 AN: 778372

Other (OTH) AF: 0.00959 AC: 348 AN: 36304

⚠️ 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: 0.0000353 AC: 3 AN: 85068 Hom.: 0 Cov.: 0 AF XY: 0.0000255 AC XY: 1 AN XY: 39158

African (AFR) AF: 0.0000466 AC: 1 AN: 21442

American (AMR) AF: 0.00 AC: 0 AN: 8056

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2376

East Asian (EAS) AF: 0.00 AC: 0 AN: 2974

South Asian (SAS) AF: 0.00 AC: 0 AN: 2316

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2732

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 128

European-Non Finnish (NFE) AF: 0.0000462 AC: 2 AN: 43308

Other (OTH) AF: 0.00 AC: 0 AN: 1096

Alfa AF: 0.00 Hom.: 238

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3
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;