dbSNP rs7995033: MTMR6:p.Ile319Val (chr13-25257750-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_004685.5(MTMR6):c.955A>G(p.Ile319Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 1,610,606 control chromosomes in the GnomAD database, including 498,503 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.63 ( 34983 hom., cov: 34)

Exomes 𝑓: 0.79 ( 463520 hom. )

Consequence

MTMR6
NM_004685.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.42

Publications

43 publications found

Variant links:

Genes affected

MTMR6 (HGNC:7453): (myotubularin related protein 6) Enables phosphatidylinositol-3,5-bisphosphate phosphatase activity and phosphatidylinositol-3-phosphatase activity. Involved in phosphatidylinositol dephosphorylation. Located in cytoplasm and nuclear envelope. [provided by Alliance of Genome Resources, Apr 2022]

MTMR6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=7.1354054E-7).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTMR6	NM_004685.5 link	c.955A>G	p.Ile319Val	missense_variant	Exon 8 of 14	ENST00000381801.6	NP_004676.3	Q9Y217-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTMR6	ENST00000381801.6 link	c.955A>G	p.Ile319Val	missense_variant	Exon 8 of 14	1	NM_004685.5	ENSP00000371221.5		Q9Y217-1
MTMR6	ENST00000482345.2 link	c.1069A>G	p.Ile357Val	missense_variant	Exon 9 of 15	5		ENSP00000516657.1		A0A9L9PXJ0

Frequencies

GnomAD3 genomes

AF:

0.627

AC:

95320

AN:

152090

Hom.:

34994

Cov.:

show subpopulations

Gnomad AFR

AF:

0.238

Gnomad AMI

AF:

0.914

Gnomad AMR

AF:

0.573

Gnomad ASJ

AF:

0.831

Gnomad EAS

AF:

0.568

Gnomad SAS

AF:

0.567

Gnomad FIN

AF:

0.841

Gnomad MID

AF:

0.782

Gnomad NFE

AF:

0.834

Gnomad OTH

AF:

0.681

GnomAD2 exomes

AF:

0.698

AC:

174703

AN:

250364

AF XY:

0.712

show subpopulations

Gnomad AFR exome

AF:

0.225

Gnomad AMR exome

AF:

0.472

Gnomad ASJ exome

AF:

0.835

Gnomad EAS exome

AF:

0.588

Gnomad FIN exome

AF:

0.844

Gnomad NFE exome

AF:

0.839

Gnomad OTH exome

AF:

0.754

GnomAD4 exome

AF:

0.786

AC:

1146230

AN:

1458398

Hom.:

463520

Cov.:

AF XY:

0.783

AC XY:

568562

AN XY:

725750

show subpopulations

African (AFR)

AF:

0.212

AC:

7069

AN:

33412

American (AMR)

AF:

0.485

AC:

21591

AN:

44494

Ashkenazi Jewish (ASJ)

AF:

0.835

AC:

21793

AN:

26104

East Asian (EAS)

AF:

0.552

AC:

21882

AN:

39614

South Asian (SAS)

AF:

0.591

AC:

50869

AN:

86106

European-Finnish (FIN)

AF:

0.838

AC:

44681

AN:

53318

Middle Eastern (MID)

AF:

0.792

AC:

4558

AN:

5754

European-Non Finnish (NFE)

AF:

0.837

AC:

928171

AN:

1109326

Other (OTH)

AF:

0.757

AC:

45616

AN:

60270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

9876

19753

29629

39506

49382

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20666

41332

61998

82664

103330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.626

AC:

95309

AN:

152208

Hom.:

34983

Cov.:

AF XY:

0.624

AC XY:

46417

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.237

AC:

9847

AN:

41514

American (AMR)

AF:

0.572

AC:

8751

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.831

AC:

2885

AN:

3470

East Asian (EAS)

AF:

0.568

AC:

2935

AN:

5166

South Asian (SAS)

AF:

0.567

AC:

2735

AN:

4826

European-Finnish (FIN)

AF:

0.841

AC:

8925

AN:

10610

Middle Eastern (MID)

AF:

0.782

AC:

230

AN:

294

European-Non Finnish (NFE)

AF:

0.834

AC:

56733

AN:

68010

Other (OTH)

AF:

0.679

AC:

1434

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1348

2696

4044

5392

6740

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

740

1480

2220

2960

3700

<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:

0.779

Hom.:

137574

Bravo

AF:

0.588

TwinsUK

AF:

0.827

AC:

3068

ALSPAC

AF:

0.830

AC:

3199

ESP6500AA

AF:

0.243

AC:

1072

ESP6500EA

AF:

0.836

AC:

7189

ExAC

AF:

0.698

AC:

84783

Asia WGS

AF:

0.549

AC:

1910

AN:

3478

EpiCase

AF:

0.827

EpiControl

AF:

0.830

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.24

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.37

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.87

MetaRNN

Benign

7.1e-7

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.27

PhyloP100

1.4

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.11

REVEL

Benign

0.23

Sift

Benign

0.61

Sift4G

Benign

0.83

Polyphen

0.0

Vest4

0.051

MPC

0.099

ClinPred

0.00063

GERP RS

3.0

Varity_R

0.037

gMVP

0.18

Mutation Taster

=98/2

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over