Variant X-150693562-G-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.32G>A(p.Gly11Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000138 in 651,235 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. 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: not found (cov: 21)

Exomes 𝑓: 0.000014 ( 0 hom. 5 hem. )

Consequence

MTMR1
NM_001306144.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.242

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21594635).

BS2

High Hemizygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTMR1	NM_001306144.3 link	c.32G>A	p.Gly11Asp	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.32G>A	p.Gly11Asp	missense_variant	1/16	1	NM_001306144.3	ENSP00000414178.2		F8WA39

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000138

AC:

AN:

651235

Hom.:

Cov.:

AF XY:

0.0000254

AC XY:

AN XY:

196591

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000152

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 04, 2024

The c.32G>A (p.G11D) alteration is located in exon 1 (coding exon 1) of the MTMR1 gene. This alteration results from a G to A substitution at nucleotide position 32, causing the glycine (G) at amino acid position 11 to be replaced by an aspartic acid (D). 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

0.25

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.26

T;.;.;T

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.34

T;T;T;T

M_CAP

Pathogenic

0.94

MetaRNN

Benign

0.22

T;T;T;T

MetaSVM

Uncertain

-0.11

MutationAssessor

Benign

0.69

N;.;.;.

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.14

N;N;N;N

REVEL

Uncertain

0.41

Sift

Benign

0.59

T;D;T;T

Sift4G

Benign

0.28

T;D;T;T

Polyphen

0.029

B;.;B;B

Vest4

0.32

MutPred

0.14

Loss of catalytic residue at G11 (P = 0.3713);Loss of catalytic residue at G11 (P = 0.3713);Loss of catalytic residue at G11 (P = 0.3713);Loss of catalytic residue at G11 (P = 0.3713);

MVP

0.88

ClinPred

0.13

GERP RS

1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.10

gMVP

0.49

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over