NM_021090.4:c.2240A>G

Variant names:

• chr22-30019899-A-G
• NM_021090.4:c.2240A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021090.4(MTMR3):​c.2240A>G​(p.Asp747Gly) variant causes a missense 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. 17/22 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)
• Consequence: MTMR3 NM_021090.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.466
• Publications: 0 publications found

Genes affected

MTMR3 (HGNC:7451): (myotubularin related protein 3) This gene encodes a member of the myotubularin dual specificity protein phosphatase gene family. The encoded protein is structurally similar to myotubularin but in addition contains a FYVE domain and an N-terminal PH-GRAM domain. The protein can self-associate and also form heteromers with another myotubularin related protein. The protein binds to phosphoinositide lipids through the PH-GRAM domain, and can hydrolyze phosphatidylinositol(3)-phosphate and phosphatidylinositol(3,5)-biphosphate in vitro. The encoded protein has been observed to have a perinuclear, possibly membrane-bound, distribution in cells, but it has also been found free in the cytoplasm. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

HORMAD2-AS1 (HGNC:50729): (HORMAD2 and MTMR3 antisense RNA 1)

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=0.09292501).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021090.4. 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
	MTMR3	NM_021090.4	MANE Select	c.2240A>G	p.Asp747Gly	missense	Exon 17 of 20	NP_066576.1	Q13615-1
	MTMR3	NM_153050.3		c.2240A>G	p.Asp747Gly	missense	Exon 17 of 20	NP_694690.1	Q13615-2
	MTMR3	NM_153051.3		c.2240A>G	p.Asp747Gly	missense	Exon 17 of 19	NP_694691.1	Q13615-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTMR3	ENST00000401950.7	TSL:1 MANE Select	c.2240A>G	p.Asp747Gly	missense	Exon 17 of 20	ENSP00000384651.3	Q13615-1
	MTMR3	ENST00000351488.7	TSL:1	c.2240A>G	p.Asp747Gly	missense	Exon 17 of 19	ENSP00000307271.6	Q13615-3
	MTMR3	ENST00000956491.1		c.2342A>G	p.Asp781Gly	missense	Exon 18 of 21	ENSP00000626550.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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	0.068
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	0.63
DANN	Benign	0.91
DEOGEN2	Benign	0.29	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.059	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-0.36	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.47
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.25
Sift	Benign	0.11	T
Sift4G	Benign	0.34	T
Polyphen		0.020	B
Vest4		0.12
MutPred		0.18		Gain of catalytic residue at P743 (P = 0.0993)
MVP		0.71
MPC		0.16
ClinPred		0.12	T
GERP RS		-4.7
Varity_R		0.092
gMVP		0.24
Mutation Taster		=95/5	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: chr22-30415888;