22-44889763-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_138415.5(PHF21B):ā€‹c.1035G>Cā€‹(p.Trp345Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,162 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)

Consequence

PHF21B
NM_138415.5 missense

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.69
Variant links:
Genes affected
PHF21B (HGNC:25161): (PHD finger protein 21B) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PHF21BNM_138415.5 linkc.1035G>C p.Trp345Cys missense_variant 9/13 ENST00000313237.10 NP_612424.1 Q96EK2-1A0A0S2Z6R3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PHF21BENST00000313237.10 linkc.1035G>C p.Trp345Cys missense_variant 9/131 NM_138415.5 ENSP00000324403.5 Q96EK2-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152162
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
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
Cov.:
30
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152162
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 27, 2023The c.1035G>C (p.W345C) alteration is located in exon 9 (coding exon 9) of the PHF21B gene. This alteration results from a G to C substitution at nucleotide position 1035, causing the tryptophan (W) at amino acid position 345 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.76
BayesDel_addAF
Benign
-0.018
T
BayesDel_noAF
Benign
-0.26
CADD
Pathogenic
33
DANN
Uncertain
0.99
DEOGEN2
Benign
0.051
.;.;T;.
Eigen
Uncertain
0.54
Eigen_PC
Uncertain
0.53
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Uncertain
0.90
D;D;D;D
M_CAP
Benign
0.027
D
MetaRNN
Uncertain
0.46
T;T;T;T
MetaSVM
Benign
-0.66
T
MutationAssessor
Benign
1.9
.;.;L;.
PrimateAI
Uncertain
0.64
T
PROVEAN
Uncertain
-3.9
D;.;D;.
REVEL
Benign
0.26
Sift
Benign
0.075
T;.;D;.
Sift4G
Benign
0.19
T;T;T;T
Polyphen
1.0
D;.;D;D
Vest4
0.62
MutPred
0.53
.;.;Loss of catalytic residue at W345 (P = 0.001);.;
MVP
0.043
MPC
1.1
ClinPred
0.98
D
GERP RS
4.5
Varity_R
0.40
gMVP
0.42

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs2070927733; hg19: chr22-45285643; API