3-9649683-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001077525.3(MTMR14):c.100G>C(p.Glu34Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: MTMR14 NM_001077525.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.41

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16535649).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTMR14	NM_001077525.3	c.100G>C	p.Glu34Gln	missense_variant	1/19	ENST00000296003.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTMR14	ENST00000296003.9	c.100G>C	p.Glu34Gln	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 specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 18, 2021

The c.100G>C (p.E34Q) alteration is located in exon 1 (coding exon 1) of the MTMR14 gene. This alteration results from a G to C substitution at nucleotide position 100, causing the glutamic acid (E) at amino acid position 34 to be replaced by a glutamine (Q). 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	0.098
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
Cadd	Benign	23
Dann	Uncertain	0.98
Eigen	Benign	0.044
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.93	D;D;D;D
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.17	T;T;T;T
MetaSVM	Uncertain	0.42	D
MutationAssessor	Benign	1.4	L;.;L;L
MutationTaster	Benign	0.66	N;N;N;N
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.0	N;N;N;N
REVEL	Uncertain	0.31
Sift	Benign	0.21	T;D;T;T
Sift4G	Benign	0.42	T;D;T;T
Polyphen		0.63	P;P;B;B
Vest4		0.18
MutPred		0.13		Gain of MoRF binding (P = 0.0541);Gain of MoRF binding (P = 0.0541);Gain of MoRF binding (P = 0.0541);Gain of MoRF binding (P = 0.0541);
MVP		0.97
MPC		0.76
ClinPred		0.81	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.11
gMVP		0.33

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: chr3-9691367;