rs2070769083

Variant names:

• chr22-44883229-G-A
• NM_138415.5:c.1453C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-44883229-G-A
• chr22-44883229-G-C
• chr22-44883229-G-T

Variant summary

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

The NM_138415.5(PHF21B):​c.1453C>T​(p.Leu485Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,644 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: PHF21B NM_138415.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.41

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF21B	NM_138415.5	c.1453C>T	p.Leu485Phe	missense_variant	Exon 13 of 13	ENST00000313237.10	NP_612424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF21B	ENST00000313237.10	c.1453C>T	p.Leu485Phe	missense_variant	Exon 13 of 13	1	NM_138415.5	ENSP00000324403.5
PHF21B	ENST00000629843.3	c.1327C>T	p.Leu443Phe	missense_variant	Exon 13 of 13	1		ENSP00000487086.1
PHF21B	ENST00000396103.7	c.1291C>T	p.Leu431Phe	missense_variant	Exon 13 of 13	2
PHF21B	ENST00000403565.5	c.841C>T	p.Leu281Phe	missense_variant	Exon 14 of 14	2		ENSP00000385053.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461644 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727136

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: 0.00000360

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.042	.;.;T;.
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.94	D;D;D;D
M_CAP	Pathogenic	0.63	D
MetaRNN	Uncertain	0.50	D;D;D;D
MetaSVM	Uncertain	0.66	D
MutationAssessor	Benign	1.6	.;.;L;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-2.1	N;.;N;.
REVEL	Uncertain	0.57
Sift	Uncertain	0.028	D;.;D;.
Sift4G	Uncertain	0.046	D;D;D;D
Polyphen		1.0	D;.;D;D
Vest4		0.62
MutPred		0.35		.;.;Loss of disorder (P = 0.0562);.;
MVP		0.48
MPC		0.99
ClinPred		0.94	D
GERP RS		3.5
Varity_R		0.27
gMVP		0.53

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: chr22-45279109;