chr6-63646802-C-A

Position:

• chr6-63646802-C-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

The NM_001370348.2(PHF3):​c.244+7C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 23)
  • Exomes 𝑓: 0.0016 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PHF3 NM_001370348.2 splice_region, intron
• Scores: Splicing: ADA: 0.01039
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.66

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 6-63646802-C-A is Benign according to our data. Variant chr6-63646802-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3045235.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHF3	NM_001370348.2	c.244+7C>A		splice_region_variant, intron_variant		ENST00000262043.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHF3	ENST00000262043.8	c.244+7C>A		splice_region_variant, intron_variant		5	NM_001370348.2	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1 AN: 76734 Hom.: 0 Cov.: 23 FAILED QC

Gnomad AFR AF: 0.0000600

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00160 AC: 1404 AN: 875770 Hom.: 0 Cov.: 29 AF XY: 0.00152 AC XY: 648 AN XY: 425134

Gnomad4 AFR exome AF: 0.000812

Gnomad4 AMR exome AF: 0.000208

Gnomad4 ASJ exome AF: 0.000649

Gnomad4 EAS exome AF: 0.000422

Gnomad4 SAS exome AF: 0.00125

Gnomad4 FIN exome AF: 0.000264

Gnomad4 NFE exome AF: 0.00177

Gnomad4 OTH exome AF: 0.00151

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000130 AC: 1 AN: 76730 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 35924

Gnomad4 AFR AF: 0.0000599

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

PHF3-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 06, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	15
DANN	Benign	0.92

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.010
dbscSNV1_RF	Benign	0.040
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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-64356707;