6-63646802-C-G

Variant names:

• chr6-63646802-C-G
• rs1192077289
• NM_001370348.2:c.244+7C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001370348.2(PHF3):​c.244+7C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000114 in 880,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: PHF3 NM_001370348.2 splice_region, intron
• Scores: Splicing: ADA: 0.01056
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.66
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF3	NM_001370348.2	c.244+7C>G		splice_region_variant, intron_variant	Intron 2 of 15	ENST00000262043.8	NP_001357277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF3	ENST00000262043.8	c.244+7C>G		splice_region_variant, intron_variant	Intron 2 of 15	5	NM_001370348.2	ENSP00000262043.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000114 AC: 1 AN: 880118 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 427146

African (AFR) AF: 0.00 AC: 0 AN: 18544

American (AMR) AF: 0.00 AC: 0 AN: 14456

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12374

East Asian (EAS) AF: 0.00 AC: 0 AN: 23716

South Asian (SAS) AF: 0.00 AC: 0 AN: 24854

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22714

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2322

European-Non Finnish (NFE) AF: 0.00000138 AC: 1 AN: 725840

Other (OTH) AF: 0.00 AC: 0 AN: 35298

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	15
DANN	Benign	0.93
PhyloP100		2.7
PromoterAI		0.013	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.011
dbscSNV1_RF	Benign	0.058
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: rs1192077289; hg19: chr6-64356707;