6-63646802-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_Moderate BP6

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 (no stars).

• 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 no assertion criteria provided B:1
• 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: Likely_benign. The variant received -3 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 no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0000130 AC: 1 AN: 76734 Hom.: 0 Cov.: 23

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

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

African (AFR) AF: 0.000812 AC: 15 AN: 18478

American (AMR) AF: 0.000208 AC: 3 AN: 14434

Ashkenazi Jewish (ASJ) AF: 0.000649 AC: 8 AN: 12330

East Asian (EAS) AF: 0.000422 AC: 10 AN: 23684

South Asian (SAS) AF: 0.00125 AC: 31 AN: 24768

European-Finnish (FIN) AF: 0.000264 AC: 6 AN: 22686

Middle Eastern (MID) AF: 0.00130 AC: 3 AN: 2316

European-Non Finnish (NFE) AF: 0.00177 AC: 1275 AN: 721956

Other (OTH) AF: 0.00151 AC: 53 AN: 35118

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

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

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

African (AFR) AF: 0.0000599 AC: 1 AN: 16696

American (AMR) AF: 0.00 AC: 0 AN: 6950

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2216

East Asian (EAS) AF: 0.00 AC: 0 AN: 2526

South Asian (SAS) AF: 0.00 AC: 0 AN: 2266

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3106

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 88

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 41250

Other (OTH) AF: 0.00 AC: 0 AN: 1040

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

PHF3-related disorder Benign:1

Dec 06, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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
PhyloP100		2.7
PromoterAI		0.0083	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1192077289; hg19: chr6-64356707;