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6-63684574-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001370348.2(PHF3):c.852A>G(p.Pro284=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00244 in 1,614,018 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0026 ( 12 hom. )

Consequence

PHF3
NM_001370348.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.474
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-63684574-A-G is Benign according to our data. Variant chr6-63684574-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3035517.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.474 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PHF3NM_001370348.2 linkuse as main transcriptc.852A>G p.Pro284= synonymous_variant 4/16 ENST00000262043.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PHF3ENST00000262043.8 linkuse as main transcriptc.852A>G p.Pro284= synonymous_variant 4/165 NM_001370348.2 P1Q92576-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00130
AC:
198
AN:
152210
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000338
Gnomad AMI
AF:
0.00548
Gnomad AMR
AF:
0.00118
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00827
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00174
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.00221
AC:
555
AN:
250678
Hom.:
4
AF XY:
0.00262
AC XY:
355
AN XY:
135618
show subpopulations
Gnomad AFR exome
AF:
0.000562
Gnomad AMR exome
AF:
0.00101
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00895
Gnomad FIN exome
AF:
0.000139
Gnomad NFE exome
AF:
0.00197
Gnomad OTH exome
AF:
0.00181
GnomAD4 exome
AF:
0.00256
AC:
3744
AN:
1461690
Hom.:
12
Cov.:
33
AF XY:
0.00272
AC XY:
1981
AN XY:
727138
show subpopulations
Gnomad4 AFR exome
AF:
0.000329
Gnomad4 AMR exome
AF:
0.00101
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00841
Gnomad4 FIN exome
AF:
0.000131
Gnomad4 NFE exome
AF:
0.00254
Gnomad4 OTH exome
AF:
0.00209
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00130
AC:
198
AN:
152328
Hom.:
2
Cov.:
32
AF XY:
0.00123
AC XY:
92
AN XY:
74506
show subpopulations
Gnomad4 AFR
AF:
0.000337
Gnomad4 AMR
AF:
0.00118
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00828
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00174
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.00186
Hom.:
0
Bravo
AF:
0.00124
Asia WGS
AF:
0.00520
AC:
18
AN:
3478
EpiCase
AF:
0.00218
EpiControl
AF:
0.00196

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

PHF3-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesDec 18, 2023This 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
-0.60
Cadd
Benign
4.4
Dann
Benign
0.52
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs41271583; hg19: chr6-64394475; COSMIC: COSV100014016; COSMIC: COSV100014016; API