1-149932297-G-A

Position:

• chr1-149932297-G-A

Variant summary

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

The NM_001145862.2(MTMR11):​c.1019C>T​(p.Ala340Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MTMR11 NM_001145862.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.59

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.1019C>T	p.Ala340Val	missense_variant	11/17	ENST00000439741.4	NP_001139334.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTMR11	ENST00000439741.4	c.1019C>T	p.Ala340Val	missense_variant	11/17	2	NM_001145862.2	ENSP00000391668.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461686 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727148

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

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

Nov 18, 2022

The c.1019C>T (p.A340V) alteration is located in exon 11 (coding exon 11) of the MTMR11 gene. This alteration results from a C to T substitution at nucleotide position 1019, causing the alanine (A) at amino acid position 340 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	0.098
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	.;T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.79	T;T
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.43	T;T
MetaSVM	Uncertain	0.45	D
MutationAssessor	Benign	1.6	.;L
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.18	N;N
REVEL	Uncertain	0.30
Sift	Benign	0.21	T;T
Sift4G	Benign	0.34	T;T
Polyphen		0.99	D;D
Vest4		0.33
MutPred		0.36		.;Gain of catalytic residue at A340 (P = 0.0609);
MVP		0.72
MPC		0.34
ClinPred		0.92	D
GERP RS		4.4
Varity_R		0.053
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs782603449; hg19: chr1-149904189;