22-44893474-C-T

Variant names:

• chr22-44893474-C-T
• rs772871332
• NM_138415.5:c.943G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_138415.5(PHF21B):​c.943G>A​(p.Gly315Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000181 in 1,601,056 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: PHF21B NM_138415.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.55
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138415.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF21B	NM_138415.5	MANE Select	c.943G>A	p.Gly315Ser	missense	Exon 7 of 13	NP_612424.1	A0A0S2Z6R3
	PHF21B	NM_001135862.3		c.817G>A	p.Gly273Ser	missense	Exon 8 of 14	NP_001129334.1	A0A0S2Z665
	PHF21B	NM_001413063.1		c.817G>A	p.Gly273Ser	missense	Exon 7 of 13	NP_001399992.1	Q96EK2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF21B	ENST00000313237.10	TSL:1 MANE Select	c.943G>A	p.Gly315Ser	missense	Exon 7 of 13	ENSP00000324403.5	Q96EK2-1
	PHF21B	ENST00000629843.3	TSL:1	c.817G>A	p.Gly273Ser	missense	Exon 7 of 13	ENSP00000487086.1	Q96EK2-3
	PHF21B	ENST00000420689.2	TSL:5	c.781G>A	p.Gly261Ser	missense	Exon 7 of 13	ENSP00000401294.2	Q96EK2-4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152148 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000219 AC: 5 AN: 228248 AF XY: 0.0000405

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000293

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000193 AC: 28 AN: 1448908 Hom.: 0 Cov.: 31 AF XY: 0.0000292 AC XY: 21 AN XY: 719466

African (AFR) AF: 0.00 AC: 0 AN: 33330

American (AMR) AF: 0.0000232 AC: 1 AN: 43174

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25820

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39320

South Asian (SAS) AF: 0.0000837 AC: 7 AN: 83610

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51864

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.0000136 AC: 15 AN: 1106118

Other (OTH) AF: 0.0000668 AC: 4 AN: 59920

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152148 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74318

African (AFR) AF: 0.0000241 AC: 1 AN: 41410

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.097	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Benign	2.0	M
PhyloP100		4.6
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-4.0	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.61
MutPred		0.25		Gain of glycosylation at G315 (P = 0.032)
MVP		0.55
MPC		0.95
ClinPred		0.94	D
GERP RS		4.6
Varity_R		0.70
gMVP		0.50
Mutation Taster		=27/73	disease causing

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

Other links and lift over

dbSNP: rs772871332; hg19: chr22-45289354;