3-9649606-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001077525.3(MTMR14):c.23C>T(p.Ala8Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MTMR14 NM_001077525.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.21

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTMR14	NM_001077525.3	c.23C>T	p.Ala8Val	missense_variant	1/19	ENST00000296003.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTMR14	ENST00000296003.9	c.23C>T	p.Ala8Val	missense_variant	1/19	1	NM_001077525.3	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Jul 21, 2023

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with MTMR14-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 8 of the MTMR14 protein (p.Ala8Val). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
Cadd	Benign	21
Dann	Uncertain	0.97
Eigen	Benign	0.018
Eigen_PC	Benign	0.083
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.85	D;T;D;D
M_CAP	Pathogenic	0.81	D
MetaRNN	Uncertain	0.68	D;D;D;D
MetaSVM	Pathogenic	0.87	D
MutationAssessor	Benign	1.8	L;.;L;L
MutationTaster	Benign	0.93	D;D;D;N
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.26	N;N;N;N
REVEL	Uncertain	0.46
Sift	Benign	0.23	T;D;T;T
Sift4G	Benign	0.17	T;D;T;T
Polyphen		0.61	P;P;P;P
Vest4		0.48
MutPred		0.38		Gain of MoRF binding (P = 0.0723);Gain of MoRF binding (P = 0.0723);Gain of MoRF binding (P = 0.0723);Gain of MoRF binding (P = 0.0723);
MVP		0.95
MPC		0.21
ClinPred		0.57	D
GERP RS		4.6
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		3.0
Varity_R		0.098
gMVP		0.47

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.

Other links and lift over

hg19: chr3-9691290;