Genetic Variant NM_021090.4:c.210+3662C>T (chr22-29982714-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021090.4(MTMR3):c.210+3662C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0407 in 152,090 control chromosomes in the GnomAD database, including 369 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.041 ( 369 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MTMR3
NM_021090.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.603

Publications

54 publications found

Variant links:

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]

MTMR3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MTMR3	NM_021090.4 link	c.210+3662C>T	intron_variant	Intron 5 of 19	ENST00000401950.7	NP_066576.1	Q13615-1
MTMR3	NM_153050.3 link	c.210+3662C>T	intron_variant	Intron 5 of 19		NP_694690.1	Q13615-2
MTMR3	NM_153051.3 link	c.210+3662C>T	intron_variant	Intron 5 of 18		NP_694691.1	Q13615-3A0A024R1I2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTMR3	ENST00000401950.7 link	c.210+3662C>T		intron_variant	Intron 5 of 19	1	NM_021090.4	ENSP00000384651.3		Q13615-1

Frequencies

GnomAD3 genomes

AF:

0.0407

AC:

6182

AN:

151972

Hom.:

368

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00982

Gnomad AMI

AF:

0.0297

Gnomad AMR

AF:

0.122

Gnomad ASJ

AF:

0.0285

Gnomad EAS

AF:

0.108

Gnomad SAS

AF:

0.244

Gnomad FIN

AF:

0.0299

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0241

Gnomad OTH

AF:

0.0427

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0407

AC:

6188

AN:

152090

Hom.:

369

Cov.:

AF XY:

0.0469

AC XY:

3489

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.00979

AC:

406

AN:

41484

American (AMR)

AF:

0.122

AC:

1862

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.0285

AC:

AN:

3470

East Asian (EAS)

AF:

0.108

AC:

561

AN:

5174

South Asian (SAS)

AF:

0.244

AC:

1175

AN:

4820

European-Finnish (FIN)

AF:

0.0299

AC:

316

AN:

10568

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0241

AC:

1639

AN:

67990

Other (OTH)

AF:

0.0432

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

282

565

847

1130

1412

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

258

344

430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0297

Hom.:

397

Bravo

AF:

0.0394

Asia WGS

AF:

0.172

AC:

596

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.8

(source)

DANN

Benign

0.49

PhyloP100

-0.60

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over