chr3-52245886-C-T

Variant names:

• chr3-52245886-C-T
• NM_144641.4:c.62C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144641.4(PPM1M):​c.62C>T​(p.Pro21Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000306 in 981,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000031 (0 hom.)
• Consequence: PPM1M NM_144641.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.755
• Publications: 0 publications found

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]

TWF2 (HGNC:9621): (twinfilin actin binding protein 2) The protein encoded by this gene was identified by its interaction with the catalytic domain of protein kinase C-zeta. The encoded protein contains an actin-binding site and an ATP-binding site. It is most closely related to twinfilin (PTK9), a conserved actin monomer-binding protein. [provided by RefSeq, Jul 2008]

ENSG00000306261 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13190302).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144641.4. 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
	PPM1M	NM_144641.4	MANE Select	c.62C>T	p.Pro21Leu	missense	Exon 1 of 10	NP_653242.3	Q96MI6-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPM1M	ENST00000323588.9	TSL:1 MANE Select	c.62C>T	p.Pro21Leu	missense	Exon 1 of 10	ENSP00000319894.5	Q96MI6-5
	PPM1M	ENST00000855772.1		c.62C>T	p.Pro21Leu	missense	Exon 1 of 10	ENSP00000525831.1
	PPM1M	ENST00000970938.1		c.62C>T	p.Pro21Leu	missense	Exon 1 of 10	ENSP00000640997.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000306 AC: 3 AN: 981370 Hom.: 0 Cov.: 30 AF XY: 0.00000630 AC XY: 3 AN XY: 476390

African (AFR) AF: 0.00 AC: 0 AN: 17946

American (AMR) AF: 0.00 AC: 0 AN: 11890

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11276

East Asian (EAS) AF: 0.00 AC: 0 AN: 4682

South Asian (SAS) AF: 0.0000388 AC: 2 AN: 51516

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8444

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2194

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 839926

Other (OTH) AF: 0.00 AC: 0 AN: 33496

GnomAD4 genome Cov.: 32

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	0.099
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0078	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.56	T
M_CAP	Pathogenic	0.38	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.76
PrimateAI	Pathogenic	0.87	D
Sift4G	Benign	0.35	T
Polyphen		0.41	B
Vest4		0.19
MutPred		0.20		Loss of glycosylation at P22 (P = 0.0065)
MVP		0.23
ClinPred		0.12	T
GERP RS		2.3
PromoterAI		0.016	Neutral
Mutation Taster		=91/9	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

hg19: chr3-52279902;