Variant chr22-44883193-C-T 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.1489G>A(p.Val497Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000192 in 1,461,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

PHF21B
NM_138415.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.72

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:

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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=0.25723004).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHF21B	NM_138415.5 linkuse as main transcript	c.1489G>A	p.Val497Ile	missense_variant	13/13	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.1489G>A	p.Val497Ile	missense_variant	13/13	1	NM_138415.5	ENSP00000324403.5	Q96EK2-1
PHF21B	ENST00000629843.3 linkuse as main transcript	c.1363G>A	p.Val455Ile	missense_variant	13/13	1		ENSP00000487086.1	Q96EK2-3
PHF21B	ENST00000396103.7 linkuse as main transcript	c.1327G>A	p.Val443Ile	missense_variant	13/13	2			Q96EK2-4
PHF21B	ENST00000403565.5 linkuse as main transcript	c.877G>A	p.Val293Ile	missense_variant	14/14	2		ENSP00000385053.2	B1AHC5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249640

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135066

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000890

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1461404

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727032

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000252

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

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

Oct 10, 2023

The c.1489G>A (p.V497I) alteration is located in exon 13 (coding exon 13) of the PHF21B gene. This alteration results from a G to A substitution at nucleotide position 1489, causing the valine (V) at amino acid position 497 to be replaced by an isoleucine (I). 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

0.15

BayesDel_addAF

Uncertain

0.047

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.014

.;.;T;.

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.88

D;D;D;D

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.26

T;T;T;T

MetaSVM

Uncertain

0.39

MutationAssessor

Benign

1.8

.;.;L;.

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.54

N;.;N;.

REVEL

Uncertain

0.37

Sift

Benign

0.040

D;.;D;.

Sift4G

Benign

0.30

T;T;T;T

Polyphen

1.0

D;.;D;D

Vest4

0.30

MutPred

0.28

.;.;Loss of glycosylation at T500 (P = 0.2194);.;

MVP

0.61

MPC

0.43

ClinPred

0.49

GERP RS

3.5

Varity_R

0.089

gMVP

0.56

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