rs562720345

Variant names:

• chr3-52247029-C-G
• rs562720345
• NM_144641.4:c.398C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-52247029-C-G
• chr3-52247029-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_144641.4(PPM1M):​c.398C>G​(p.Ala133Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000067 in 1,551,512 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (1 hom., cov: 32)
  • Exomes 𝑓: 0.000066 (0 hom.)
• Consequence: PPM1M NM_144641.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.18
• 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]

ENSG00000306261 (HGNC:):

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.076018155).

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.398C>G	p.Ala133Gly	missense	Exon 3 of 10	NP_653242.3	Q96MI6-5
	PPM1M	NM_001122870.3		c.-40+217C>G		intron	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.398C>G	p.Ala133Gly	missense	Exon 3 of 10	ENSP00000319894.5	Q96MI6-5
	PPM1M	ENST00000409502.7	TSL:1	c.-40+217C>G		intron	N/A	ENSP00000387046.3	Q96MI6-4
	PPM1M	ENST00000855772.1		c.398C>G	p.Ala133Gly	missense	Exon 3 of 10	ENSP00000525831.1

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152200 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000956 AC: 15 AN: 156974 AF XY: 0.000109

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000438

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000820

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000665 AC: 93 AN: 1399194 Hom.: 0 Cov.: 32 AF XY: 0.0000724 AC XY: 50 AN XY: 690210

African (AFR) AF: 0.00 AC: 0 AN: 31652

American (AMR) AF: 0.00 AC: 0 AN: 35748

Ashkenazi Jewish (ASJ) AF: 0.000238 AC: 6 AN: 25168

East Asian (EAS) AF: 0.00101 AC: 36 AN: 35786

South Asian (SAS) AF: 0.000240 AC: 19 AN: 79250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48692

Middle Eastern (MID) AF: 0.000703 AC: 4 AN: 5688

European-Non Finnish (NFE) AF: 0.0000222 AC: 24 AN: 1079176

Other (OTH) AF: 0.0000689 AC: 4 AN: 58034

GnomAD4 genome AF: 0.0000722 AC: 11 AN: 152318 Hom.: 1 Cov.: 32 AF XY: 0.0000806 AC XY: 6 AN XY: 74482

African (AFR) AF: 0.00 AC: 0 AN: 41560

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5182

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000453

ExAC AF: 0.0000474 AC: 5

Asia WGS AF: 0.000866 AC: 3 AN: 3478

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	Pathogenic	0.59
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.063	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-1.1	T
PhyloP100		6.2
PrimateAI	Uncertain	0.62	T
Sift4G	Uncertain	0.0090	D
Polyphen		0.99	D
Vest4		0.66
MVP		0.46
ClinPred		0.17	T
GERP RS		4.5
PromoterAI		-0.36	Neutral
Mutation Taster		=264/36	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs562720345; hg19: chr3-52281045;