11-95845106-C-A

Position:

• chr11-95845106-C-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6 BP7

The NM_016156.6(MTMR2):​c.1233G>T​(p.Thr411=) variant causes a synonymous 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 Benign (no stars). Synonymous variant affecting the same amino acid position (i.e. T411T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MTMR2 NM_016156.6 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -4.40

Genes affected

MTMR2 (HGNC:7450): (myotubularin related protein 2) This gene is a member of the myotubularin family of phosphoinositide lipid phosphatases. The encoded protein possesses phosphatase activity towards phosphatidylinositol-3-phosphate and phosphatidylinositol-3,5-bisphosphate. Mutations in this gene are a cause of Charcot-Marie-Tooth disease type 4B, an autosomal recessive demyelinating neuropathy. Alternatively spliced transcript variants encoding multiple isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 11-95845106-C-A is Benign according to our data. Variant chr11-95845106-C-A is described in ClinVar as [Benign]. Clinvar id is 637887.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-95845106-C-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-4.4 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTMR2	NM_016156.6	c.1233G>T	p.Thr411=	synonymous_variant	11/15	ENST00000346299.10	NP_057240.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTMR2	ENST00000346299.10	c.1233G>T	p.Thr411=	synonymous_variant	11/15	1	NM_016156.6	ENSP00000345752	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

not specified Benign:1

Benign, no assertion criteria provided

literature only

Inherited Neuropathy Consortium

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- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.020
DANN	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs113897932; hg19: chr11-95578270;