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. The variant received -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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). 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: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.90
• 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: Likely_benign. The variant received -2 ACMG points.

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

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.1504A>G	p.Thr502Ala	missense	Exon 13 of 13	NP_612424.1	A0A0S2Z6R3
	PHF21B	NM_001135862.3		c.1378A>G	p.Thr460Ala	missense	Exon 14 of 14	NP_001129334.1	A0A0S2Z665
	PHF21B	NM_001413063.1		c.1378A>G	p.Thr460Ala	missense	Exon 13 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.1504A>G	p.Thr502Ala	missense	Exon 13 of 13	ENSP00000324403.5	Q96EK2-1
	PHF21B	ENST00000629843.3	TSL:1	c.1378A>G	p.Thr460Ala	missense	Exon 13 of 13	ENSP00000487086.1	Q96EK2-3
	PHF21B	ENST00000420689.2	TSL:5	c.1342A>G	p.Thr448Ala	missense	Exon 13 of 13	ENSP00000401294.2	Q96EK2-4

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

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52856

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111974

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.063
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
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.9
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.24
Sift	Benign	0.48	T
Sift4G	Benign	0.46	T
Polyphen		0.0030	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
Mutation Taster		=71/29	polymorphism

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: rs201377055; hg19: chr22-45279058;