Variant 3-9649593-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000296003.9(MTMR14):c.10G>A(p.Ala4Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000502 in 1,393,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

MTMR14
ENST00000296003.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.62

Variant links:

Genes affected

MTMR14 (HGNC:26190): (myotubularin related protein 14) This gene encodes a myotubularin-related protein. The encoded protein is a phosphoinositide phosphatase that specifically dephosphorylates phosphatidylinositol 3,5-biphosphate and phosphatidylinositol 3-phosphate. Mutations in this gene are correlated with autosomal dominant centronuclear myopathy. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 18.[provided by RefSeq, Apr 2010]

MTMR14 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21993822).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTMR14	NM_001077525.3 linkuse as main transcript	c.10G>A	p.Ala4Thr	missense_variant	1/19	ENST00000296003.9	NP_001070993.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTMR14	ENST00000296003.9 linkuse as main transcript	c.10G>A	p.Ala4Thr	missense_variant	1/19	1	NM_001077525.3	ENSP00000296003	P2	Q8NCE2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000502

AC:

AN:

1393076

Hom.:

Cov.:

AF XY:

0.00000291

AC XY:

AN XY:

686694

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000281

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000464

Gnomad4 OTH exome

AF:

0.0000173

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

Nov 09, 2021

The c.10G>A (p.A4T) alteration is located in exon 1 (coding exon 1) of the MTMR14 gene. This alteration results from a G to A substitution at nucleotide position 10, causing the alanine (A) at amino acid position 4 to be replaced by a threonine (T). 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

0.31

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0086

.;T;T;.

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.74

T;T;T;T

M_CAP

Pathogenic

0.49

MetaRNN

Benign

0.22

T;T;T;T

MetaSVM

Uncertain

0.71

MutationAssessor

Benign

0.69

N;.;N;N

MutationTaster

Benign

0.64

D;D;D;N

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.20

N;N;N;N

REVEL

Uncertain

0.45

Sift

Benign

0.032

D;D;D;D

Sift4G

Uncertain

0.043

D;D;T;D

Polyphen

0.010

B;B;B;B

Vest4

0.25

MutPred

0.29

Loss of helix (P = 0.028);Loss of helix (P = 0.028);Loss of helix (P = 0.028);Loss of helix (P = 0.028);

MVP

0.92

MPC

0.21

ClinPred

0.44

GERP RS

4.4

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.061

gMVP

0.37

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