Variant X-150730566-T-A 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.699T>A(p.Asn233Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000213 in 1,171,060 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000023 ( 0 hom. 15 hem. )

Consequence

MTMR1
NM_001306144.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.27

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21450749).

BS2

High Hemizygotes in GnomAdExome4 at 15 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTMR1	NM_001306144.3 linkuse as main transcript	c.699T>A	p.Asn233Lys	missense_variant	8/16	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.699T>A	p.Asn233Lys	missense_variant	8/16	1	NM_001306144.3	ENSP00000414178.2		F8WA39

Frequencies

GnomAD3 genomes

AF:

0.00000890

AC:

AN:

112399

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

34553

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:

0.000364

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000419

AC:

AN:

167138

Hom.:

AF XY:

0.0000918

AC XY:

AN XY:

54446

show subpopulations

Gnomad AFR exome

AF:

0.0000820

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000386

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000227

AC:

AN:

1058661

Hom.:

Cov.:

AF XY:

0.0000450

AC XY:

AN XY:

333591

show subpopulations

Gnomad4 AFR exome

AF:

0.0000393

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000452

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000450

GnomAD4 genome

AF:

0.00000890

AC:

AN:

112399

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

34553

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:

0.000364

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000824

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

Dec 28, 2022

The c.675T>A (p.N225K) alteration is located in exon 7 (coding exon 7) of the MTMR1 gene. This alteration results from a T to A substitution at nucleotide position 675, causing the asparagine (N) at amino acid position 225 to be replaced by a lysine (K). 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

Uncertain

0.42

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.41

T;D;.;D

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.96

D;D;D;D

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.21

T;T;T;T

MetaSVM

Uncertain

-0.14

MutationAssessor

Benign

1.9

.;L;.;.

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-4.1

D;D;D;D

REVEL

Benign

0.26

Sift

Uncertain

0.0030

D;D;T;D

Sift4G

Benign

0.093

T;T;D;T

Polyphen

0.22, 0.16, 0.038

.;B;B;B

Vest4

0.22, 0.18, 0.14

MutPred

0.55

.;.;.;Gain of methylation at N233 (P = 0.0157);

MVP

0.93

ClinPred

0.16

GERP RS

-0.24

Varity_R

0.76

gMVP

0.57

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