NM_138415.5:c.1504A>G

Variant names:

• chr22-44883178-T-C
• rs201377055
• NM_138415.5:c.1504A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_138415.5(PHF21B):​c.1504A>G​(p.Thr502Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. T502P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PHF21B NM_138415.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.90

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.051992744).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF21B	NM_138415.5	c.1504A>G	p.Thr502Ala	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.1504A>G	p.Thr502Ala	missense_variant	Exon 13 of 13	1	NM_138415.5	ENSP00000324403.5
PHF21B	ENST00000629843.3	c.1378A>G	p.Thr460Ala	missense_variant	Exon 13 of 13	1		ENSP00000487086.1
PHF21B	ENST00000396103.7	c.1342A>G	p.Thr448Ala	missense_variant	Exon 13 of 13	2
PHF21B	ENST00000403565.5	c.892A>G	p.Thr298Ala	missense_variant	Exon 14 of 14	2		ENSP00000385053.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461170 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726924

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	12
DANN	Benign	0.72
DEOGEN2	Benign	0.0014	.;.;T;.
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.77
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.58	T;T;T;T
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.052	T;T;T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.5	.;.;L;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.39	N;.;N;.
REVEL	Benign	0.24
Sift	Benign	0.48	T;.;T;.
Sift4G	Benign	0.46	T;T;T;T
Polyphen		0.0030	B;.;B;B
Vest4		0.086
MutPred		0.10		.;.;Loss of glycosylation at T502 (P = 0.0503);.;
MVP		0.13
MPC		0.27
ClinPred		0.18	T
GERP RS		0.12
Varity_R		0.054
gMVP		0.63

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

LitVar

Other links and lift over

dbSNP: rs201377055; hg19: chr22-45279058;