22-44888071-G-T

Position:

• chr22-44888071-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138415.5(PHF21B):​c.1089C>A​(p.Asn363Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PHF21B NM_138415.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.59

Genes affected

PHF21B (HGNC:25161): (PHD finger protein 21B) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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=0.2523287).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHF21B	NM_138415.5	c.1089C>A	p.Asn363Lys	missense_variant	10/13	ENST00000313237.10	NP_612424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHF21B	ENST00000313237.10	c.1089C>A	p.Asn363Lys	missense_variant	10/13	1	NM_138415.5	ENSP00000324403.5
PHF21B	ENST00000629843.3	c.963C>A	p.Asn321Lys	missense_variant	10/13	1		ENSP00000487086.1
PHF21B	ENST00000396103.7	c.927C>A	p.Asn309Lys	missense_variant	10/13	2
PHF21B	ENST00000403565.5	c.477C>A	p.Asn159Lys	missense_variant	11/14	2		ENSP00000385053.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1397032 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 689180

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 29, 2024

The c.1089C>A (p.N363K) alteration is located in exon 10 (coding exon 10) of the PHF21B gene. This alteration results from a C to A substitution at nucleotide position 1089, causing the asparagine (N) at amino acid position 363 to be replaced by a lysine (K). 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	0.22
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0058	.;.;T;.
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.65	T;T;T;T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.25	T;T;T;T
MetaSVM	Uncertain	-0.043	T
MutationAssessor	Benign	0.89	.;.;L;.
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.81	N;.;N;.
REVEL	Benign	0.20
Sift	Benign	0.081	T;.;D;.
Sift4G	Benign	0.15	T;T;T;T
Polyphen		0.44	B;.;P;B
Vest4		0.40
MutPred		0.58		.;.;Gain of methylation at N363 (P = 0.0292);.;
MVP		0.28
MPC		0.39
ClinPred		0.23	T
GERP RS		2.0
Varity_R		0.11
gMVP		0.16

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-45283951;