Variant chr22-44913934-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_138415.5(PHF21B):c.719C>T(p.Thr240Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000565 in 1,592,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

PHF21B
NM_138415.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.50

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]

PHF21B links:

PHF21B (HGNC:):

PHF21B links:

Genome browser will be placed here

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=0.10613525).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHF21B	NM_138415.5 linkuse as main transcript	c.719C>T	p.Thr240Met	missense_variant	5/13	ENST00000313237.10	NP_612424.1	Q96EK2-1A0A0S2Z6R3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHF21B	ENST00000313237.10 linkuse as main transcript	c.719C>T	p.Thr240Met	missense_variant	5/13	1	NM_138415.5	ENSP00000324403.5		Q96EK2-1

Frequencies

GnomAD3 genomes

AF:

0.0000199

AC:

AN:

150464

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

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

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251144

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135754

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000603

AC:

AN:

1442446

Hom.:

Cov.:

AF XY:

0.0000516

AC XY:

AN XY:

717340

show subpopulations

Gnomad4 AFR exome

AF:

0.0000304

Gnomad4 AMR exome

AF:

0.0000453

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000259

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000728

Gnomad4 OTH exome

AF:

0.0000339

GnomAD4 genome

AF:

0.0000199

AC:

AN:

150464

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73454

show subpopulations

Gnomad4 AFR

AF:

0.0000244

Gnomad4 AMR

AF:

0.000132

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

Alfa

AF:

0.0000676

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000247

AC:

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 submitter

clinical testing

Ambry Genetics

Dec 16, 2022

The c.719C>T (p.T240M) alteration is located in exon 5 (coding exon 5) of the PHF21B gene. This alteration results from a C to T substitution at nucleotide position 719, causing the threonine (T) at amino acid position 240 to be replaced by a methionine (M). 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

Benign

0.093

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0072

.;.;T;.;.;.

Eigen

Benign

0.098

Eigen_PC

Benign

0.059

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.90

D;D;D;D;D;D

M_CAP

Benign

0.021

MetaRNN

Benign

0.11

T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.5

.;.;L;.;.;.

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.9

N;.;N;.;N;N

REVEL

Benign

0.086

Sift

Uncertain

0.0020

D;.;D;.;D;D

Sift4G

Benign

0.064

T;D;D;D;.;.

Polyphen

0.99

D;.;D;P;.;.

Vest4

0.39

MutPred

0.11

.;.;Loss of phosphorylation at T240 (P = 0.029);.;.;.;

MVP

0.20

MPC

0.72

ClinPred

0.45

GERP RS

3.7

Varity_R

0.064

gMVP

0.70

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over