Variant chr22-44888091-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_138415.5(PHF21B):c.1069G>T(p.Ala357Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000499 in 1,544,526 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

PHF21B
NM_138415.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.08

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.020407349).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHF21B	NM_138415.5 linkuse as main transcript	c.1069G>T	p.Ala357Ser	missense_variant	10/13	ENST00000313237.10	NP_612424.1	Q96EK2-1A0A0S2Z6R3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PHF21B	ENST00000313237.10 linkuse as main transcript	c.1069G>T	p.Ala357Ser	missense_variant	10/13	1	NM_138415.5	ENSP00000324403.5	Q96EK2-1
PHF21B	ENST00000629843.3 linkuse as main transcript	c.943G>T	p.Ala315Ser	missense_variant	10/13	1		ENSP00000487086.1	Q96EK2-3
PHF21B	ENST00000396103.7 linkuse as main transcript	c.907G>T	p.Ala303Ser	missense_variant	10/13	2			Q96EK2-4
PHF21B	ENST00000403565.5 linkuse as main transcript	c.457G>T	p.Ala153Ser	missense_variant	11/14	2		ENSP00000385053.2	B1AHC5

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00366

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000299

AC:

AN:

150350

Hom.:

AF XY:

0.000239

AC XY:

AN XY:

79512

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00414

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000409

AC:

AN:

1392202

Hom.:

Cov.:

AF XY:

0.0000350

AC XY:

AN XY:

686634

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00147

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000868

GnomAD4 genome

AF:

0.000131

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00367

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000151

ExAC

AF:

0.000175

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

Aug 22, 2023

The c.1069G>T (p.A357S) alteration is located in exon 10 (coding exon 10) of the PHF21B gene. This alteration results from a G to T substitution at nucleotide position 1069, causing the alanine (A) at amino acid position 357 to be replaced by a serine (S). 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

0.096

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.018

.;.;T;.

Eigen

Benign

0.041

Eigen_PC

Benign

0.053

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.85

T;T;T;T

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.020

T;T;T;T

MetaSVM

Uncertain

0.58

MutationAssessor

Benign

0.76

.;.;N;.

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.7

N;.;N;.

REVEL

Uncertain

0.38

Sift

Benign

0.030

D;.;D;.

Sift4G

Uncertain

0.010

D;D;D;D

Polyphen

0.62

P;.;D;P

Vest4

0.22

MutPred

0.45

.;.;Gain of disorder (P = 0.0699);.;

MVP

0.49

MPC

0.50

ClinPred

0.067

GERP RS

3.0

Varity_R

0.15

gMVP

0.23

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