chr5-32229807-C-A

Variant names:

• chr5-32229807-C-A
• rs1374917487
• NM_001040446.3:c.2215G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001040446.3(MTMR12):​c.2215G>T​(p.Asp739Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MTMR12 NM_001040446.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.17
• Publications: 0 publications found

Genes affected

MTMR12 (HGNC:18191): (myotubularin related protein 12) Phosphatidylinositide 3-kinase-derived membrane-anchored phosphatidylinositides, such as phosphatidylinositol 3-phosphate (PtdIns(3)P), regulate diverse cellular processes. The protein encoded by this gene functions as an adaptor subunit in a complex with an active PtdIns(3)P 3-phosphatase. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.784

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040446.3. 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
	MTMR12	NM_001040446.3	MANE Select	c.2215G>T	p.Asp739Tyr	missense	Exon 16 of 16	NP_001035536.1	Q9C0I1-1
	MTMR12	NM_001294343.2		c.2053G>T	p.Asp685Tyr	missense	Exon 15 of 15	NP_001281272.1	Q9C0I1-2
	MTMR12	NM_001294344.2		c.1885G>T	p.Asp629Tyr	missense	Exon 14 of 14	NP_001281273.1	Q9C0I1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTMR12	ENST00000382142.8	TSL:1 MANE Select	c.2215G>T	p.Asp739Tyr	missense	Exon 16 of 16	ENSP00000371577.3	Q9C0I1-1
	MTMR12	ENST00000280285.9	TSL:1	c.2053G>T	p.Asp685Tyr	missense	Exon 15 of 15	ENSP00000280285.5	Q9C0I1-2
	MTMR12	ENST00000851378.1		c.2359G>T	p.Asp787Tyr	missense	Exon 17 of 17	ENSP00000521437.1

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	Uncertain	0.48
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.23
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Pathogenic	0.49	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Pathogenic	1.2	D
MutationAssessor	Benign	0.97	L
PhyloP100		6.2
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.64
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.60
MutPred		0.39		Loss of disorder (P = 9e-04)
MVP		0.76
MPC		1.5
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.56
gMVP		0.77
Mutation Taster		=52/48	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: rs1374917487; hg19: chr5-32229913;