Variant X-150693582-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001306144.3(MTMR1):c.52C>G(p.Pro18Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000408 in 759,120 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., 6 hem., cov: 22)

Exomes 𝑓: 0.000017 ( 0 hom. 1 hem. )

Consequence

MTMR1
NM_001306144.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.48

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18558523).

BS2

High Hemizygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTMR1	NM_001306144.3 link	c.52C>G	p.Pro18Ala	missense_variant	1/16	ENST00000445323.7	NP_001293073.1	F8WA39

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTMR1	ENST00000445323.7 link	c.52C>G	p.Pro18Ala	missense_variant	1/16	1	NM_001306144.3	ENSP00000414178.2		F8WA39

Frequencies

GnomAD3 genomes

AF:

0.000185

AC:

AN:

107835

Hom.:

Cov.:

AF XY:

0.000184

AC XY:

AN XY:

32569

show subpopulations

Gnomad AFR

AF:

0.000591

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000191

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000169

AC:

AN:

651285

Hom.:

Cov.:

AF XY:

0.00000510

AC XY:

AN XY:

196007

show subpopulations

Gnomad4 AFR exome

AF:

0.000397

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000787

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000229

GnomAD4 genome

AF:

0.000185

AC:

AN:

107835

Hom.:

Cov.:

AF XY:

0.000184

AC XY:

AN XY:

32569

show subpopulations

Gnomad4 AFR

AF:

0.000591

Gnomad4 AMR

AF:

0.000191

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000166

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

Apr 19, 2024

The c.52C>G (p.P18A) alteration is located in exon 1 (coding exon 1) of the MTMR1 gene. This alteration results from a C to G substitution at nucleotide position 52, causing the proline (P) at amino acid position 18 to be replaced by an alanine (A). 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

0.053

BayesDel_addAF

Uncertain

0.081

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.26

T;.;.;T

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.51

T;T;T;T

M_CAP

Pathogenic

0.76

MetaRNN

Benign

0.19

T;T;T;T

MetaSVM

Uncertain

-0.24

MutationAssessor

Benign

0.41

N;.;.;.

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.14

N;N;N;N

REVEL

Benign

0.29

Sift

Benign

0.18

T;D;T;T

Sift4G

Benign

0.68

T;T;T;T

Polyphen

0.0030

B;.;B;B

Vest4

0.32

MutPred

0.15

Loss of glycosylation at P20 (P = 0.1311);Loss of glycosylation at P20 (P = 0.1311);Loss of glycosylation at P20 (P = 0.1311);Loss of glycosylation at P20 (P = 0.1311);

MVP

0.82

ClinPred

0.051

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.048

gMVP

0.27

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

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