rs1041261270

Variant names:

• chr3-52245993-C-T
• rs1041261270
• NM_144641.4:c.169C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-52245993-C-T
• chr3-52245993-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_144641.4(PPM1M):​c.169C>T​(p.Pro57Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000263 in 152,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PPM1M NM_144641.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.51
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31860197).

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.169C>T	p.Pro57Ser	missense	Exon 1 of 10	NP_653242.3	Q96MI6-5
	PPM1M	NM_001122870.3		c.-479C>T		upstream_gene	N/A	NP_001116342.1	Q96MI6-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPM1M	ENST00000323588.9	TSL:1 MANE Select	c.169C>T	p.Pro57Ser	missense	Exon 1 of 10	ENSP00000319894.5	Q96MI6-5
	PPM1M	ENST00000855772.1		c.169C>T	p.Pro57Ser	missense	Exon 1 of 10	ENSP00000525831.1
	PPM1M	ENST00000970938.1		c.169C>T	p.Pro57Ser	missense	Exon 1 of 10	ENSP00000640997.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152010 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1091470 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 534594

African (AFR) AF: 0.00 AC: 0 AN: 19976

American (AMR) AF: 0.00 AC: 0 AN: 22040

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14542

East Asian (EAS) AF: 0.00 AC: 0 AN: 7812

South Asian (SAS) AF: 0.00 AC: 0 AN: 70644

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 13858

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3516

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 899640

Other (OTH) AF: 0.00 AC: 0 AN: 39442

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152010 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74242

African (AFR) AF: 0.0000965 AC: 4 AN: 41432

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5138

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67966

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

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	0.12
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.093	T
Eigen	Uncertain	0.29
Eigen_PC	Benign	0.17
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.56	T
M_CAP	Pathogenic	0.81	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.44	T
PhyloP100		1.5
PrimateAI	Pathogenic	0.90	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.15
MutPred		0.24		Gain of glycosylation at S60 (P = 0.0128)
MVP		0.31
ClinPred		0.35	T
GERP RS		3.3
PromoterAI		-0.037	Neutral
Mutation Taster		=85/15	polymorphism

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

Other links and lift over

dbSNP: rs1041261270; hg19: chr3-52280009;