Variant X-150718626-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001306144.3(MTMR1):c.278C>G(p.Ala93Gly) variant causes a missense, splice region change. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000029 ( 0 hom., 1 hem., cov: 13)

Exomes 𝑓: 0.00038 ( 0 hom. 26 hem. )

Failed GnomAD Quality Control

Consequence

MTMR1
NM_001306144.3 missense, splice_region

Scores

Splicing: ADA: 0.5780

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.08

Variant links:

Genes affected

MTMR1 (HGNC:7449): (myotubularin related protein 1) This gene encodes a member of the myotubularin related family of proteins. Members of this family contain the consensus sequence for the active site of protein tyrosine phosphatases. Alternatively spliced variants have been described but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

MTMR1 links:

MTMR1 (HGNC:):

MTMR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.24816254).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTMR1	NM_001306144.3 linkuse as main transcript	c.278C>G	p.Ala93Gly	missense_variant, splice_region_variant	4/16	ENST00000445323.7	NP_001293073.1	F8WA39

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTMR1	ENST00000445323.7 linkuse as main transcript	c.278C>G	p.Ala93Gly	missense_variant, splice_region_variant	4/16	1	NM_001306144.3	ENSP00000414178.2		F8WA39

Frequencies

GnomAD3 genomes

AF:

0.0000292

AC:

AN:

68569

Hom.:

Cov.:

AF XY:

0.0000791

AC XY:

AN XY:

12635

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00121

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000249

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000218

AC:

AN:

137301

Hom.:

AF XY:

0.0000250

AC XY:

AN XY:

40031

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000457

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000378

AC:

113

AN:

299255

Hom.:

Cov.:

AF XY:

0.000254

AC XY:

AN XY:

102203

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000455

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000829

Gnomad4 SAS exome

AF:

0.000223

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000562

Gnomad4 OTH exome

AF:

0.000151

GnomAD4 genome

AF:

0.0000292

AC:

AN:

68595

Hom.:

Cov.:

AF XY:

0.0000791

AC XY:

AN XY:

12649

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00121

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000249

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2022

The c.254C>G (p.A85G) alteration is located in exon 3 (coding exon 3) of the MTMR1 gene. This alteration results from a C to G substitution at nucleotide position 254, causing the alanine (A) at amino acid position 85 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.28

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

T;.;.;T;T;T

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.63

T;T;T;T;T;T

M_CAP

Pathogenic

0.69

MetaRNN

Benign

0.25

T;T;T;T;T;T

MetaSVM

Uncertain

-0.19

MutationAssessor

Benign

1.9

L;.;.;.;.;.

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.93

N;N;N;N;N;N

REVEL

Uncertain

0.50

Sift

Benign

0.41

T;T;T;T;T;D

Sift4G

Benign

0.28

T;D;T;T;D;D

Polyphen

0.0020

B;.;B;B;.;.

Vest4

0.40

MutPred

0.36

.;.;.;Loss of stability (P = 0.0334);.;.;

MVP

1.0

ClinPred

0.16

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.25

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.58

dbscSNV1_RF

Benign

0.43

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over