22-44888034-G-A

Position:

• chr22-44888034-G-A

Variant summary

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

The NM_138415.5(PHF21B):​c.1126C>T​(p.Leu376Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000071 in 1,409,382 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: 7.1e-7 (0 hom.)
• Consequence: PHF21B NM_138415.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.70

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 (HGNC:):

ACMG classification

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	c.1126C>T	p.Leu376Phe	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.1126C>T	p.Leu376Phe	missense_variant	10/13	1	NM_138415.5	ENSP00000324403.5
PHF21B	ENST00000629843.3	c.1000C>T	p.Leu334Phe	missense_variant	10/13	1		ENSP00000487086.1
PHF21B	ENST00000396103.7	c.964C>T	p.Leu322Phe	missense_variant	10/13	2
PHF21B	ENST00000403565.5	c.514C>T	p.Leu172Phe	missense_variant	11/14	2		ENSP00000385053.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.10e-7 AC: 1 AN: 1409382 Hom.: 0 Cov.: 32 AF XY: 0.00000144 AC XY: 1 AN XY: 696318

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: 9.21e-7

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

Dec 03, 2021

The c.1126C>T (p.L376F) alteration is located in exon 10 (coding exon 10) of the PHF21B gene. This alteration results from a C to T substitution at nucleotide position 1126, causing the leucine (L) at amino acid position 376 to be replaced by a phenylalanine (F). 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	0.19
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.068	.;.;T;.
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.96	D;D;D;D
M_CAP	Benign	0.083	D
MetaRNN	Uncertain	0.49	T;T;T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.3	.;.;L;.
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.2	D;D;D;.
REVEL	Uncertain	0.36
Sift	Uncertain	0.0010	D;D;D;.
Sift4G	Uncertain	0.013	D;D;D;D
Polyphen		1.0	D;.;D;P
Vest4		0.58
MutPred		0.52		.;.;Loss of disorder (P = 0.0973);.;
MVP		0.83
MPC		0.99
ClinPred		0.98	D
GERP RS		4.1
Varity_R		0.54
gMVP		0.18

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: chr22-45283914;