X-134377740-G-A
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6_Very_StrongBP7
The NM_001015877.2(PHF6):c.123G>A(p.Ala41=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000995 in 1,206,007 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000037 ( 0 hom., 1 hem., cov: 22)
Exomes 𝑓: 0.0000073 ( 0 hom. 5 hem. )
Consequence
PHF6
NM_001015877.2 synonymous
NM_001015877.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.12
Genes affected
PHF6 (HGNC:18145): (PHD finger protein 6) This gene is a member of the plant homeodomain (PHD)-like finger (PHF) family. It encodes a protein with two PHD-type zinc finger domains, indicating a potential role in transcriptional regulation, that localizes to the nucleolus. Mutations affecting the coding region of this gene or the splicing of the transcript have been associated with Borjeson-Forssman-Lehmann syndrome (BFLS), a disorder characterized by cognitive disability, epilepsy, hypogonadism, hypometabolism, obesity, swelling of subcutaneous tissue of the face, narrow palpebral fissures, and large ears. Alternate splicing results in multiple transcript variants, encoding different isoforms. [provided by RefSeq, Jun 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
?
Variant X-134377740-G-A is Benign according to our data. Variant chrX-134377740-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1757918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=3.12 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHF6 | NM_001015877.2 | c.123G>A | p.Ala41= | synonymous_variant | 2/11 | ENST00000370803.8 | |
PHF6 | NM_032458.3 | c.123G>A | p.Ala41= | synonymous_variant | 2/10 | ||
PHF6 | NM_032335.3 | c.123G>A | p.Ala41= | synonymous_variant | 2/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHF6 | ENST00000370803.8 | c.123G>A | p.Ala41= | synonymous_variant | 2/11 | 1 | NM_001015877.2 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000366 AC: 4AN: 109264Hom.: 0 Cov.: 22 AF XY: 0.0000316 AC XY: 1AN XY: 31670
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GnomAD3 exomes AF: 0.00000547 AC: 1AN: 182980Hom.: 0 AF XY: 0.0000148 AC XY: 1AN XY: 67542
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GnomAD4 exome AF: 0.00000729 AC: 8AN: 1096743Hom.: 0 Cov.: 29 AF XY: 0.0000138 AC XY: 5AN XY: 362167
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
PHF6-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 05, 2020 | 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). - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 30, 2018 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at