22-44883182-C-G

Variant names:

• chr22-44883182-C-G
• rs771448144
• NM_138415.5:c.1500G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_138415.5(PHF21B):​c.1500G>C​(p.Thr500Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T500T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PHF21B NM_138415.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.32
• 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP7: Synonymous conserved (PhyloP=-2.32 with no splicing effect.

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.1500G>C	p.Thr500Thr	synonymous	Exon 13 of 13	NP_612424.1	A0A0S2Z6R3
	PHF21B	NM_001135862.3		c.1374G>C	p.Thr458Thr	synonymous	Exon 14 of 14	NP_001129334.1	A0A0S2Z665
	PHF21B	NM_001413063.1		c.1374G>C	p.Thr458Thr	synonymous	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.1500G>C	p.Thr500Thr	synonymous	Exon 13 of 13	ENSP00000324403.5	Q96EK2-1
	PHF21B	ENST00000629843.3	TSL:1	c.1374G>C	p.Thr458Thr	synonymous	Exon 13 of 13	ENSP00000487086.1	Q96EK2-3
	PHF21B	ENST00000420689.2	TSL:5	c.1338G>C	p.Thr446Thr	synonymous	Exon 13 of 13	ENSP00000401294.2	Q96EK2-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461180 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726934

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52870

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111974

Other (OTH) AF: 0.0000166 AC: 1 AN: 60376

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.2
DANN	Benign	0.57
PhyloP100		-2.3

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: rs771448144; hg19: chr22-45279062;