22-44891347-G-A

Variant names:

• chr22-44891347-G-A
• NM_138415.5:c.974C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_138415.5(PHF21B):​c.974C>T​(p.Ala325Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: PHF21B NM_138415.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.66

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33610702).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF21B	NM_138415.5	c.974C>T	p.Ala325Val	missense_variant	Exon 8 of 13	ENST00000313237.10	NP_612424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF21B	ENST00000313237.10	c.974C>T	p.Ala325Val	missense_variant	Exon 8 of 13	1	NM_138415.5	ENSP00000324403.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 17, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.974C>T (p.A325V) alteration is located in exon 8 (coding exon 8) of the PHF21B gene. This alteration results from a C to T substitution at nucleotide position 974, causing the alanine (A) at amino acid position 325 to be replaced by a valine (V). 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	0.23
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.029	.;.;T;.;.
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.97	D;D;D;D;D
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.34	T;T;T;T;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.9	.;.;L;.;.
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.6	D;.;N;.;D
REVEL	Benign	0.20
Sift	Benign	0.088	T;.;T;.;D
Sift4G	Uncertain	0.0050	D;D;D;D;.
Polyphen		0.83	P;.;P;P;.
Vest4		0.67
MutPred		0.29		.;.;Loss of disorder (P = 0.0491);.;.;
MVP		0.24
MPC		0.38
ClinPred		0.98	D
GERP RS		4.9
Varity_R		0.17
gMVP		0.41

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: chr22-45287227;