3-52246766-G-T

Variant names:

• chr3-52246766-G-T
• ENST00000409502.7:c.-86G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001122870.3(PPM1M):​c.-86G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPM1M NM_001122870.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.186
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06262654).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001122870.3. 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.296G>T	p.Cys99Phe	missense	Exon 2 of 10	NP_653242.3	Q96MI6-5
	PPM1M	NM_001122870.3		c.-86G>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 9	NP_001116342.1	Q96MI6-4
	PPM1M	NM_001122870.3		c.-86G>T		5_prime_UTR	Exon 2 of 9	NP_001116342.1	Q96MI6-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPM1M	ENST00000409502.7	TSL:1	c.-86G>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 9	ENSP00000387046.3	Q96MI6-4
	PPM1M	ENST00000323588.9	TSL:1 MANE Select	c.296G>T	p.Cys99Phe	missense	Exon 2 of 10	ENSP00000319894.5	Q96MI6-5
	PPM1M	ENST00000409502.7	TSL:1	c.-86G>T		5_prime_UTR	Exon 2 of 9	ENSP00000387046.3	Q96MI6-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	0.075
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	10
DANN	Benign	0.61
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.19
PrimateAI	Benign	0.30	T
Sift4G	Benign	0.65	T
Polyphen		0.20	B
Vest4		0.12
MutPred		0.34		Loss of sheet (P = 0.0315)
MVP		0.19
ClinPred		0.050	T
GERP RS		-0.69
PromoterAI		0.010	Neutral
Mutation Taster		=97/3	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: chr3-52280782;