1-149929700-G-T

Position:

• chr1-149929700-G-T

Variant summary

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

The NM_001145862.2(MTMR11):​c.1864C>A​(p.Leu622Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 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: MTMR11 NM_001145862.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.19

Genes affected

MTMR11 (HGNC:24307): (myotubularin related protein 11) Predicted to enable phosphatidylinositol-3-phosphatase activity. Predicted to be involved in phosphatidylinositol dephosphorylation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MTMR11 (HGNC:):

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	Protein	UniProt
MTMR11	NM_001145862.2	c.1864C>A	p.Leu622Met	missense_variant	16/17	ENST00000439741.4	NP_001139334.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTMR11	ENST00000439741.4	c.1864C>A	p.Leu622Met	missense_variant	16/17	2	NM_001145862.2	ENSP00000391668.2

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

Apr 26, 2024

The c.1864C>A (p.L622M) alteration is located in exon 16 (coding exon 16) of the MTMR11 gene. This alteration results from a C to A substitution at nucleotide position 1864, causing the leucine (L) at amino acid position 622 to be replaced by a methionine (M). 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	0.18
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.040	.;T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.71	T;T
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.46	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.6	.;L
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.85	N;N
REVEL	Benign	0.19
Sift	Uncertain	0.0030	D;D
Sift4G	Benign	0.15	T;T
Polyphen		1.0	D;D
Vest4		0.42
MutPred		0.38		.;Loss of glycosylation at P619 (P = 0.2233);
MVP		0.71
MPC		0.71
ClinPred		0.78	D
GERP RS		3.1
Varity_R		0.23
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr1-149901592;