dbSNP rs17646919: MTMR3:c.671+1879A>G (chr22-30004872-A-G) – 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.671+1879A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0532 in 152,362 control chromosomes in the GnomAD database, including 311 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 0.053 ( 311 hom., cov: 32)

Exomes 𝑓: 0.067 ( 0 hom. )

Consequence

MTMR3
NM_021090.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.158

Publications

9 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=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
MTMR3	NM_021090.4 link	c.671+1879A>G	intron_variant	Intron 9 of 19	ENST00000401950.7	NP_066576.1
MTMR3	NM_153050.3 link	c.671+1879A>G	intron_variant	Intron 9 of 19		NP_694690.1
MTMR3	NM_153051.3 link	c.671+1879A>G	intron_variant	Intron 9 of 18		NP_694691.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTMR3	ENST00000401950.7 link	c.671+1879A>G		intron_variant	Intron 9 of 19	1	NM_021090.4	ENSP00000384651.3

Frequencies

GnomAD3 genomes

AF:

0.0533

AC:

8106

AN:

152214

Hom.:

312

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0139

Gnomad AMI

AF:

0.123

Gnomad AMR

AF:

0.0728

Gnomad ASJ

AF:

0.0718

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00973

Gnomad FIN

AF:

0.0460

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0787

Gnomad OTH

AF:

0.0736

GnomAD4 exome

AF:

0.0667

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0556

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0769

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0532

AC:

8101

AN:

152332

Hom.:

311

Cov.:

AF XY:

0.0499

AC XY:

3721

AN XY:

74510

show subpopulations

African (AFR)

AF:

0.0138

AC:

576

AN:

41590

American (AMR)

AF:

0.0728

AC:

1113

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0718

AC:

249

AN:

3466

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.00995

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0460

AC:

489

AN:

10624

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0786

AC:

5347

AN:

68024

Other (OTH)

AF:

0.0724

AC:

153

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

393

786

1180

1573

1966

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<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:

0.0739

Hom.:

1091

Bravo

AF:

0.0572

Asia WGS

AF:

0.00808

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.68

(source)

DANN

Benign

0.67

PhyloP100

-0.16

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