rs750532972

Variant names:

• chr22-44888043-C-A
• rs750532972
• NM_138415.5:c.1117G>T

Your query was ambiguous. Multiple possible variants found:

• chr22-44888043-C-A
• chr22-44888043-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_138415.5(PHF21B):​c.1117G>T​(p.Ala373Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. A373T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PHF21B NM_138415.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.63

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31105623).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF21B	NM_138415.5	c.1117G>T	p.Ala373Ser	missense_variant	Exon 10 of 13	ENST00000313237.10	NP_612424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF21B	ENST00000313237.10	c.1117G>T	p.Ala373Ser	missense_variant	Exon 10 of 13	1	NM_138415.5	ENSP00000324403.5
PHF21B	ENST00000629843.3	c.991G>T	p.Ala331Ser	missense_variant	Exon 10 of 13	1		ENSP00000487086.1
PHF21B	ENST00000396103.7	c.955G>T	p.Ala319Ser	missense_variant	Exon 10 of 13	2
PHF21B	ENST00000403565.5	c.505G>T	p.Ala169Ser	missense_variant	Exon 11 of 14	2		ENSP00000385053.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1403862 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 693126

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: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ExAC AF: 0.0000267 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	.;.;T;.
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.96	D;D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.31	T;T;T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	1.3	.;.;L;.
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-2.0	N;.;N;.
REVEL	Benign	0.24
Sift	Benign	0.13	T;.;T;.
Sift4G	Uncertain	0.057	T;T;T;T
Polyphen		1.0	D;.;D;D
Vest4		0.36
MutPred		0.43		.;.;Gain of disorder (P = 0.0508);.;
MVP		0.19
MPC		0.32
ClinPred		0.96	D
GERP RS		4.0
Varity_R		0.26
gMVP		0.29

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: rs750532972; hg19: chr22-45283923;