rs746179699

Variant names:

• chr22-44885448-C-A
• NM_138415.5:c.1355G>T

Your query was ambiguous. Multiple possible variants found:

• chr22-44885448-C-A
• chr22-44885448-C-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.1355G>T​(p.Arg452Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,436,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R452Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: PHF21B NM_138415.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.95

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=0.24028057).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF21B	NM_138415.5	c.1355G>T	p.Arg452Leu	missense_variant	Exon 12 of 13	ENST00000313237.10	NP_612424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF21B	ENST00000313237.10	c.1355G>T	p.Arg452Leu	missense_variant	Exon 12 of 13	1	NM_138415.5	ENSP00000324403.5
PHF21B	ENST00000629843.3	c.1229G>T	p.Arg410Leu	missense_variant	Exon 12 of 13	1		ENSP00000487086.1
PHF21B	ENST00000396103.7	c.1193G>T	p.Arg398Leu	missense_variant	Exon 12 of 13	2
PHF21B	ENST00000403565.5	c.743G>T	p.Arg248Leu	missense_variant	Exon 13 of 14	2		ENSP00000385053.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1436134 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 712240

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: 0.0000168

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0096	.;.;T;.
Eigen	Benign	0.064
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.93	D;D;D;D
M_CAP	Uncertain	0.087	D
MetaRNN	Benign	0.24	T;T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.2	.;.;L;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.3	D;.;D;.
REVEL	Benign	0.11
Sift	Uncertain	0.0070	D;.;D;.
Sift4G	Uncertain	0.011	D;D;D;D
Polyphen		0.51	P;.;P;P
Vest4		0.56
MutPred		0.18		.;.;Loss of MoRF binding (P = 0.0256);.;
MVP		0.17
MPC		0.79
ClinPred		0.94	D
GERP RS		4.3
Varity_R		0.27
gMVP		0.38

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: chr22-45281328;