Genetic Variant PHF21B:p.Glu243Lys (chr22-44913926-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138415.5(PHF21B):c.727G>A(p.Glu243Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000239 in 1,466,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

PHF21B
NM_138415.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.82

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15395376).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138415.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PHF21B	NM_138415.5	MANE Select	c.727G>A	p.Glu243Lys	missense	Exon 5 of 13	NP_612424.1	A0A0S2Z6R3
PHF21B	NM_001135862.3		c.601G>A	p.Glu201Lys	missense	Exon 6 of 14	NP_001129334.1	A0A0S2Z665
PHF21B	NM_001413063.1		c.601G>A	p.Glu201Lys	missense	Exon 5 of 13	NP_001399992.1	Q96EK2-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PHF21B	ENST00000313237.10	TSL:1 MANE Select	c.727G>A	p.Glu243Lys	missense	Exon 5 of 13	ENSP00000324403.5	Q96EK2-1
PHF21B	ENST00000629843.3	TSL:1	c.601G>A	p.Glu201Lys	missense	Exon 5 of 13	ENSP00000487086.1	Q96EK2-3
PHF21B	ENST00000420689.2	TSL:5	c.565G>A	p.Glu189Lys	missense	Exon 5 of 13	ENSP00000401294.2	Q96EK2-4

Frequencies

GnomAD3 genomes

AF:

0.0000138

AC:

AN:

144888

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000252

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000693

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

GnomAD2 exomes

AF:

0.0000199

AC:

AN:

251210

AF XY:

0.0000221

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.0000250

AC:

AN:

1321862

Hom.:

Cov.:

AF XY:

0.0000290

AC XY:

AN XY:

656262

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29356

American (AMR)

AF:

0.00

AC:

AN:

40404

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20688

East Asian (EAS)

AF:

0.00

AC:

AN:

27412

South Asian (SAS)

AF:

0.0000235

AC:

AN:

84996

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41736

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5046

European-Non Finnish (NFE)

AF:

0.0000274

AC:

AN:

1021336

Other (OTH)

AF:

0.0000590

AC:

AN:

50888

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000138

AC:

AN:

144888

Hom.:

Cov.:

AF XY:

0.0000142

AC XY:

AN XY:

70338

show subpopulations

African (AFR)

AF:

0.0000252

AC:

AN:

39714

American (AMR)

AF:

0.0000693

AC:

AN:

14436

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3382

East Asian (EAS)

AF:

0.00

AC:

AN:

4502

South Asian (SAS)

AF:

0.00

AC:

AN:

4216

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9184

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66232

Other (OTH)

AF:

0.00

AC:

AN:

2030

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0055

Eigen

Benign

0.094

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.020

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.6

PhyloP100

1.8

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.4

REVEL

Benign

0.097

Sift

Uncertain

0.0010

Sift4G

Benign

0.42

Polyphen

0.86

Vest4

0.29

MVP

0.10

MPC

0.52

ClinPred

0.22

GERP RS

3.6

Varity_R

0.18

gMVP

0.61

Mutation Taster

=87/13

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over