rs375528061

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005392.4(PHF2):​c.504G>C​(p.Lys168Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,399,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

PHF2
NM_005392.4 missense

Scores

1
4
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0780
Variant links:
Genes affected
PHF2 (HGNC:8920): (PHD finger protein 2) This gene encodes a protein which contains a zinc finger-like PHD (plant homeodomain) finger, distinct from other classes of zinc finger motifs, and a hydrophobic and highly conserved domain. The PHD finger shows the typical Cys4-His-Cys3 arrangement. PHD finger genes are thought to belong to a diverse group of transcriptional regulators possibly affecting eukaryotic gene expression by influencing chromatin structure. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.18521306).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PHF2NM_005392.4 linkc.504G>C p.Lys168Asn missense_variant Exon 5 of 22 ENST00000359246.9 NP_005383.3 O75151

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PHF2ENST00000359246.9 linkc.504G>C p.Lys168Asn missense_variant Exon 5 of 22 1 NM_005392.4 ENSP00000352185.4 O75151
PHF2ENST00000610682.1 linkc.239+12649G>C intron_variant Intron 3 of 7 5 ENSP00000479936.1 A0A087WW48
PHF2ENST00000375376.8 linkc.187-4153G>C intron_variant Intron 3 of 8 5 E7ET14

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000214
AC:
3
AN:
1399436
Hom.:
0
Cov.:
32
AF XY:
0.00000290
AC XY:
2
AN XY:
690228
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000278
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.39
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.026
T
Eigen
Benign
-0.17
Eigen_PC
Benign
-0.15
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Uncertain
0.93
D
M_CAP
Benign
0.028
D
MetaRNN
Benign
0.19
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.6
L
PrimateAI
Pathogenic
0.79
T
PROVEAN
Benign
-0.99
N
REVEL
Benign
0.13
Sift
Benign
0.13
T
Sift4G
Benign
0.080
T
Polyphen
0.90
P
Vest4
0.24
MutPred
0.40
Gain of ubiquitination at K166 (P = 0.0291);
MVP
0.38
MPC
0.63
ClinPred
0.81
D
GERP RS
0.29
Varity_R
0.40
gMVP
0.84

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-96411396; API