NM_001370348.2:c.244+25_244+33delTTTTTTTTT

Variant names:

• chr6-63646806-CTTTTTTTTT-C
• rs11285703
• NM_001370348.2:c.244+25_244+33delTTTTTTTTT

Variant summary

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

The NM_001370348.2(PHF3):​c.244+25_244+33delTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000323 in 928,454 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: not found (cov: 0)
  • Exomes 𝑓: 0.0000032 (0 hom.)
• Consequence: PHF3 NM_001370348.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.23
• 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 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF3	NM_001370348.2	MANE Select	c.244+25_244+33delTTTTTTTTT		intron	N/A	NP_001357277.1	Q92576-1
	PHF3	NM_015153.4		c.244+25_244+33delTTTTTTTTT		intron	N/A	NP_055968.1	Q92576-1
	PHF3	NM_001290259.2		c.-214+25_-214+33delTTTTTTTTT		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+20delTTTTTTTTT		intron	N/A	ENSP00000262043.4	Q92576-1
	PHF3	ENST00000393387.5	TSL:1	c.244+12_244+20delTTTTTTTTT		intron	N/A	ENSP00000377048.1	Q92576-1
	PHF3	ENST00000506783.5	TSL:1	c.-153+10657_-153+10665delTTTTTTTTT		intron	N/A	ENSP00000424694.1	E7EVH3

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000323 AC: 3 AN: 928454 Hom.: 0 AF XY: 0.00000226 AC XY: 1 AN XY: 442344

⚠️ 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: 19272

American (AMR) AF: 0.00 AC: 0 AN: 9848

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12030

East Asian (EAS) AF: 0.0000435 AC: 1 AN: 22996

South Asian (SAS) AF: 0.00 AC: 0 AN: 18568

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2434

European-Non Finnish (NFE) AF: 0.00000254 AC: 2 AN: 787124

Other (OTH) AF: 0.00 AC: 0 AN: 36818

⚠️ 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.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.2

Splicing

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

Other links and lift over

dbSNP: rs11285703; hg19: chr6-64356711;