chr3-52247719-A-C

Variant names:

• chr3-52247719-A-C
• NM_144641.4:c.635A>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_144641.4(PPM1M):​c.635A>C​(p.Gln212Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000698 in 1,433,462 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Q212R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: PPM1M NM_144641.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.17

Genes affected

PPM1M (HGNC:26506): (protein phosphatase, Mg2+/Mn2+ dependent 1M) Predicted to enable manganese ion binding activity and phosphoprotein phosphatase activity. Predicted to be involved in protein dephosphorylation. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPM1M	NM_144641.4	c.635A>C	p.Gln212Pro	missense_variant	Exon 4 of 10	ENST00000323588.9	NP_653242.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPM1M	ENST00000323588.9	c.635A>C	p.Gln212Pro	missense_variant	Exon 4 of 10	1	NM_144641.4	ENSP00000319894.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1433462 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 711818

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000233

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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T;T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.85	T;D
M_CAP	Benign	0.0078	T
MetaRNN	Uncertain	0.68	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	.;L
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.2	.;N
REVEL	Benign	0.17
Sift	Benign	0.33	.;T
Sift4G	Benign	0.34	T;T
Polyphen		1.0	D;P
Vest4		0.75
MutPred		0.41		Loss of glycosylation at S210 (P = 0.0786);.;
MVP		0.51
ClinPred		0.87	D
GERP RS		4.0
Varity_R		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr3-52281735;