Genetic Variant PHF21B:p.His351Gln (chr22-44888107-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_138415.5(PHF21B):c.1053C>G(p.His351Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000241 in 1,532,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

PHF21B
NM_138415.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.09

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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12795371).

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.1053C>G	p.His351Gln	missense	Exon 10 of 13	NP_612424.1	A0A0S2Z6R3
PHF21B	NM_001135862.3		c.927C>G	p.His309Gln	missense	Exon 11 of 14	NP_001129334.1	A0A0S2Z665
PHF21B	NM_001413063.1		c.927C>G	p.His309Gln	missense	Exon 10 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.1053C>G	p.His351Gln	missense	Exon 10 of 13	ENSP00000324403.5	Q96EK2-1
PHF21B	ENST00000629843.3	TSL:1	c.927C>G	p.His309Gln	missense	Exon 10 of 13	ENSP00000487086.1	Q96EK2-3
PHF21B	ENST00000420689.2	TSL:5	c.891C>G	p.His297Gln	missense	Exon 10 of 13	ENSP00000401294.2	Q96EK2-4

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000506

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

GnomAD2 exomes

AF:

0.00000721

AC:

AN:

138726

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000130

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1380630

Hom.:

Cov.:

AF XY:

0.0000103

AC XY:

AN XY:

680428

show subpopulations

African (AFR)

AF:

0.000486

AC:

AN:

30856

American (AMR)

AF:

0.00

AC:

AN:

33918

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24598

East Asian (EAS)

AF:

0.00

AC:

AN:

34468

South Asian (SAS)

AF:

0.00

AC:

AN:

77114

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48054

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4240

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1070300

Other (OTH)

AF:

0.0000175

AC:

AN:

57082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.434

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:

0.000138

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.000506

AC:

AN:

41472

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68042

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

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:

0.0000712

Hom.:

Bravo

AF:

0.000181

ExAC

AF:

0.0000200

AC:

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

0.16

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.11

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.71

M_CAP

Benign

0.016

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.92

MutationAssessor

Benign

2.0

PhyloP100

-1.1

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-5.3

REVEL

Benign

0.24

Sift

Uncertain

0.029

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.45

MutPred

0.41

Gain of methylation at K346 (P = 0.1477)

MVP

0.24

MPC

0.33

ClinPred

0.39

GERP RS

-4.2

Varity_R

0.51

gMVP

0.17

Mutation Taster

=65/35

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