22-30019592-C-T

Variant names:

• chr22-30019592-C-T
• rs138823197
• NM_021090.4:c.1933C>T

Variant summary

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

The NM_021090.4(MTMR3):​c.1933C>T​(p.Arg645Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000308 in 1,613,820 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00032 (0 hom.)
• Consequence: MTMR3 NM_021090.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.38
• Publications: 2 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.

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.1933C>T	p.Arg645Trp	missense	Exon 17 of 20	NP_066576.1	Q13615-1
	MTMR3	NM_153050.3		c.1933C>T	p.Arg645Trp	missense	Exon 17 of 20	NP_694690.1	Q13615-2
	MTMR3	NM_153051.3		c.1933C>T	p.Arg645Trp	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.1933C>T	p.Arg645Trp	missense	Exon 17 of 20	ENSP00000384651.3	Q13615-1
	MTMR3	ENST00000351488.7	TSL:1	c.1933C>T	p.Arg645Trp	missense	Exon 17 of 19	ENSP00000307271.6	Q13615-3
	MTMR3	ENST00000956491.1		c.2035C>T	p.Arg679Trp	missense	Exon 18 of 21	ENSP00000626550.1

Frequencies

GnomAD3 genomes AF: 0.000191 AC: 29 AN: 152224 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000184 AC: 46 AN: 249338 AF XY: 0.000185

Gnomad AFR exome AF: 0.0000637

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000274

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000328

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000320 AC: 468 AN: 1461596 Hom.: 0 Cov.: 30 AF XY: 0.000294 AC XY: 214 AN XY: 727118

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000671 AC: 3 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000655 AC: 26 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53124

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.000379 AC: 422 AN: 1112012

Other (OTH) AF: 0.000232 AC: 14 AN: 60394

GnomAD4 genome AF: 0.000191 AC: 29 AN: 152224 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74362

African (AFR) AF: 0.000121 AC: 5 AN: 41456

American (AMR) AF: 0.0000654 AC: 1 AN: 15282

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000323 AC: 22 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000316 Hom.: 0

Bravo AF: 0.000249

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000206 AC: 25

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000356

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	0.23
BayesDel_addAF	Benign	-0.0015	T
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.74	D
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Uncertain	0.53	D
MutationAssessor	Benign	2.0	M
PhyloP100		1.4
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-4.3	D
REVEL	Uncertain	0.57
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.99	D
Vest4		0.66
MVP		0.73
MPC		0.55
ClinPred		0.25	T
GERP RS		1.3
Varity_R		0.21
gMVP		0.54
Mutation Taster		=67/33	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: rs138823197; hg19: chr22-30415581;