6-63684119-CCT-C

Variant names:

• chr6-63684119-CCT-C
• rs138127805
• NM_001370348.2:c.407-9_407-8delCT

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_001370348.2(PHF3):​c.407-9_407-8delCT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0135 in 1,563,428 control chromosomes in the GnomAD database, including 170 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.010 (14 hom., cov: 32)
  • Exomes 𝑓: 0.014 (156 hom.)
• Consequence: PHF3 NM_001370348.2 splice_region, intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.10

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 Benign. Variant got -9 ACMG points.

• BP6: Variant 6-63684119-CCT-C is Benign according to our data. Variant chr6-63684119-CCT-C is described in ClinVar as [Benign]. Clinvar id is 3037746.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00999 (1518/152008) while in subpopulation NFE AF= 0.0159 (1077/67938). AF 95% confidence interval is 0.0151. There are 14 homozygotes in gnomad4. There are 742 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 14 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF3	NM_001370348.2	c.407-9_407-8delCT		splice_region_variant, intron_variant	Intron 3 of 15	ENST00000262043.8	NP_001357277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF3	ENST00000262043.8	c.407-9_407-8delCT		splice_region_variant, intron_variant	Intron 3 of 15	5	NM_001370348.2	ENSP00000262043.4

Frequencies

GnomAD3 genomes AF: 0.0100 AC: 1519 AN: 151890 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.00319

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00420

Gnomad ASJ AF: 0.00894

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0189

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0159

Gnomad OTH AF: 0.00527

GnomAD3 exomes AF: 0.00993 AC: 2141 AN: 215666 Hom.: 9 AF XY: 0.00994 AC XY: 1166 AN XY: 117342

Gnomad AFR exome AF: 0.00189

Gnomad AMR exome AF: 0.00231

Gnomad ASJ exome AF: 0.0100

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0168

Gnomad NFE exome AF: 0.0156

Gnomad OTH exome AF: 0.00721

GnomAD4 exome AF: 0.0139 AC: 19647 AN: 1411420 Hom.: 156 AF XY: 0.0135 AC XY: 9459 AN XY: 700386

Gnomad4 AFR exome AF: 0.00149

Gnomad4 AMR exome AF: 0.00247

Gnomad4 ASJ exome AF: 0.00910

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000889

Gnomad4 FIN exome AF: 0.0159

Gnomad4 NFE exome AF: 0.0164

Gnomad4 OTH exome AF: 0.0101

GnomAD4 genome AF: 0.00999 AC: 1518 AN: 152008 Hom.: 14 Cov.: 32 AF XY: 0.00998 AC XY: 742 AN XY: 74324

Gnomad4 AFR AF: 0.00318

Gnomad4 AMR AF: 0.00419

Gnomad4 ASJ AF: 0.00894

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0189

Gnomad4 NFE AF: 0.0159

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.0110 Hom.: 5

Bravo AF: 0.00830

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

PHF3-related disorder Benign:1

Sep 05, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as 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

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

Publications

LitVar

Other links and lift over

dbSNP: rs138127805; hg19: chr6-64394020;