chr11-45934077-T-C
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBS1BS2
The NM_001352027.3(PHF21A):c.1937A>G(p.Asn646Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00047 in 1,613,976 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0028 ( 16 hom., cov: 32)
Exomes 𝑓: 0.00023 ( 7 hom. )
Consequence
PHF21A
NM_001352027.3 missense
NM_001352027.3 missense
Scores
6
11
Clinical Significance
Conservation
PhyloP100: 3.66
Genes affected
PHF21A (HGNC:24156): (PHD finger protein 21A) The PHF21A gene encodes BHC80, a component of a BRAF35 (MIM 605535)/histone deacetylase (HDAC; see MIM 601241) complex (BHC) that mediates repression of neuron-specific genes through the cis-regulatory element known as repressor element-1 (RE1) or neural restrictive silencer (NRS) (Hakimi et al., 2002 [PubMed 12032298]).[supplied by OMIM, Nov 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, PHF21A
BP4
?
Computational evidence support a benign effect (MetaRNN=0.007928789).
BP6
?
Variant 11-45934077-T-C is Benign according to our data. Variant chr11-45934077-T-C is described in ClinVar as [Benign]. Clinvar id is 1618357.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00276 (420/152182) while in subpopulation AMR AF= 0.0268 (410/15278). AF 95% confidence interval is 0.0247. There are 16 homozygotes in gnomad4. There are 293 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 420 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHF21A | NM_001352027.3 | c.1937A>G | p.Asn646Ser | missense_variant | 19/19 | ENST00000676320.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHF21A | ENST00000676320.1 | c.1937A>G | p.Asn646Ser | missense_variant | 19/19 | NM_001352027.3 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00276 AC: 420AN: 152064Hom.: 16 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000894 AC: 224AN: 250564Hom.: 5 AF XY: 0.000922 AC XY: 125AN XY: 135566
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GnomAD4 exome AF: 0.000232 AC: 339AN: 1461794Hom.: 7 Cov.: 32 AF XY: 0.000245 AC XY: 178AN XY: 727202
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GnomAD4 genome ? AF: 0.00276 AC: 420AN: 152182Hom.: 16 Cov.: 32 AF XY: 0.00394 AC XY: 293AN XY: 74412
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
PHF21A-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 01, 2021 | 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Uncertain
D;D;T
Sift4G
Benign
T;T;.
Polyphen
P;P;.
Vest4
MVP
MPC
0.16
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at