Variant 22-44888043-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_138415.5(PHF21B):c.1117G>A(p.Ala373Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000057 in 1,403,862 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

PHF21B
NM_138415.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.63

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHF21B	NM_138415.5 link	c.1117G>A	p.Ala373Thr	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 link	c.1117G>A	p.Ala373Thr	missense_variant	10/13	1	NM_138415.5	ENSP00000324403.5	Q96EK2-1
PHF21B	ENST00000629843.3 link	c.991G>A	p.Ala331Thr	missense_variant	10/13	1		ENSP00000487086.1	Q96EK2-3
PHF21B	ENST00000396103.7 link	c.955G>A	p.Ala319Thr	missense_variant	10/13	2			Q96EK2-4
PHF21B	ENST00000403565.5 link	c.505G>A	p.Ala169Thr	missense_variant	11/14	2		ENSP00000385053.2	B1AHC5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000187

AC:

AN:

160782

Hom.:

AF XY:

0.0000351

AC XY:

AN XY:

85578

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:

0.0000319

Gnomad OTH exome

AF:

0.000228

GnomAD4 exome

AF:

0.00000570

AC:

AN:

1403862

Hom.:

Cov.:

AF XY:

0.0000101

AC XY:

AN XY:

693126

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:

0.00000739

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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 21, 2024

The c.1117G>A (p.A373T) alteration is located in exon 10 (coding exon 10) of the PHF21B gene. This alteration results from a G to A substitution at nucleotide position 1117, causing the alanine (A) at amino acid position 373 to be replaced by a threonine (T). 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

0.12

BayesDel_addAF

Uncertain

0.012

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.0097

.;.;T;.

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.97

D;D;D;D

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.50

D;D;D;D

MetaSVM

Benign

-0.39

MutationAssessor

Uncertain

2.0

.;.;M;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.4

N;.;N;.

REVEL

Benign

0.27

Sift

Benign

0.082

T;.;D;.

Sift4G

Benign

0.070

T;T;T;T

Polyphen

1.0

D;.;D;D

Vest4

0.63

MutPred

0.43

.;.;Gain of phosphorylation at T369 (P = 0.1133);.;

MVP

0.17

MPC

0.36

ClinPred

0.60

GERP RS

4.0

Varity_R

0.25

gMVP

0.33

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