rs1559446069

Variant names:

• chr3-52246011-C-G
• rs1559446069
• NM_144641.4:c.187C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-52246011-C-G
• chr3-52246011-C-A

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.187C>G​(p.Arg63Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000065 in 1,077,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/15 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: 0.0000065 (0 hom.)
• Consequence: PPM1M NM_144641.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.49
• 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=0.19219893).

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.187C>G	p.Arg63Gly	missense	Exon 1 of 10	NP_653242.3	Q96MI6-5
	PPM1M	NM_001122870.3		c.-461C>G		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.187C>G	p.Arg63Gly	missense	Exon 1 of 10	ENSP00000319894.5	Q96MI6-5
	PPM1M	ENST00000855772.1		c.187C>G	p.Arg63Gly	missense	Exon 1 of 10	ENSP00000525831.1
	PPM1M	ENST00000970938.1		c.187C>G	p.Arg63Gly	missense	Exon 1 of 10	ENSP00000640997.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000650 AC: 7 AN: 1077444 Hom.: 0 Cov.: 31 AF XY: 0.00000949 AC XY: 5 AN XY: 527032

African (AFR) AF: 0.0000517 AC: 1 AN: 19324

American (AMR) AF: 0.00 AC: 0 AN: 18756

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13688

East Asian (EAS) AF: 0.00 AC: 0 AN: 7692

South Asian (SAS) AF: 0.00 AC: 0 AN: 68566

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14140

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3680

European-Non Finnish (NFE) AF: 0.00000672 AC: 6 AN: 892920

Other (OTH) AF: 0.00 AC: 0 AN: 38678

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	0.073
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.60	T
M_CAP	Pathogenic	0.41	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.97	T
PhyloP100		2.5
PrimateAI	Pathogenic	0.91	D
Sift4G	Benign	0.30	T
Polyphen		0.15	B
Vest4		0.24
MutPred		0.35		Loss of MoRF binding (P = 0.0105)
MVP		0.15
ClinPred		0.65	D
GERP RS		3.5
PromoterAI		0.22	Neutral
Mutation Taster		=90/10	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

dbSNP: rs1559446069; hg19: chr3-52280027;