8-17304461-G-C

Variant summary

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

The NM_004686.5(MTMR7):c.1411C>G(p.Leu471Val) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MTMR7 NM_004686.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0960

Genes affected

MTMR7 (HGNC:7454): (myotubularin related protein 7) This gene encodes a member of the myotubularin family of tyrosine/dual-specificity phosphatases. The encoded protein is characterized by four distinct domains that are conserved among all members of the myotubularin family: the glucosyltransferase, Rab-like GTPase activator and myotubularins domain, the Rac-induced recruitment domain, the protein tyrosine phosphatases and dual-specificity phosphatases domain and the suppressor of variegation 3-9, enhancer-of-zeste, and trithorax interaction domain. This protein dephosphorylates the target substrates phosphatidylinositol 3-phosphate and inositol 1,3-bisphosphate. A pseudogene of this gene is found on chromosome 5. [provided by RefSeq, Mar 2009]

VPS37A (HGNC:):

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=0.16905704).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTMR7	NM_004686.5	c.1411C>G	p.Leu471Val	missense_variant	12/14	ENST00000180173.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTMR7	ENST00000180173.10	c.1411C>G	p.Leu471Val	missense_variant	12/14	1	NM_004686.5	P1
MTMR7	ENST00000521857.5	c.1411C>G	p.Leu471Val	missense_variant	12/13	5
MTMR7	ENST00000519590.5	n.423C>G		non_coding_transcript_exon_variant	3/4	4
MTMR7	ENST00000519763.1	n.547C>G		non_coding_transcript_exon_variant	5/5	4

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

Feb 27, 2023

The c.1411C>G (p.L471V) alteration is located in exon 12 (coding exon 12) of the MTMR7 gene. This alteration results from a C to G substitution at nucleotide position 1411, causing the leucine (L) at amino acid position 471 to be replaced by a valine (V). 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	0.069
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
Cadd	Benign	3.5
Dann	Benign	0.96
DEOGEN2	Benign	0.16	T;.
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.3	L;L
MutationTaster	Benign	0.96	D;D;D
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.56	N;N
REVEL	Benign	0.24
Sift	Benign	0.42	T;T
Sift4G	Benign	0.43	T;T
Polyphen		0.0	B;B
Vest4		0.23
MutPred		0.25		Gain of MoRF binding (P = 0.0899);Gain of MoRF binding (P = 0.0899);
MVP		0.65
MPC		0.019
ClinPred		0.052	T
GERP RS		-3.6
Varity_R		0.047
gMVP		0.44

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: chr8-17161970;