rs11205303

Variant names:

• chr1-149934520-T-C
• rs11205303
• NM_001145862.2:c.475A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145862.2(MTMR11):​c.475A>G​(p.Met159Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 1,613,058 control chromosomes in the GnomAD database, including 116,305 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.29 (7829 hom., cov: 32)
  • Exomes 𝑓: 0.38 (108476 hom.)
• Consequence: MTMR11 NM_001145862.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.555

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0030397177).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTMR11	NM_001145862.2	c.475A>G	p.Met159Val	missense_variant	Exon 6 of 17	ENST00000439741.4	NP_001139334.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTMR11	ENST00000439741.4	c.475A>G	p.Met159Val	missense_variant	Exon 6 of 17	2	NM_001145862.2	ENSP00000391668.2

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44016 AN: 152008 Hom.: 7833 Cov.: 32

Gnomad AFR AF: 0.0800

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.340

GnomAD3 exomes AF: 0.333 AC: 83545 AN: 251124 Hom.: 15140 AF XY: 0.344 AC XY: 46658 AN XY: 135722

Gnomad AFR exome AF: 0.0685

Gnomad AMR exome AF: 0.240

Gnomad ASJ exome AF: 0.285

Gnomad EAS exome AF: 0.332

Gnomad SAS exome AF: 0.330

Gnomad FIN exome AF: 0.307

Gnomad NFE exome AF: 0.408

Gnomad OTH exome AF: 0.354

GnomAD4 exome AF: 0.379 AC: 553189 AN: 1460928 Hom.: 108476 Cov.: 40 AF XY: 0.378 AC XY: 275039 AN XY: 726822

Gnomad4 AFR exome AF: 0.0649

Gnomad4 AMR exome AF: 0.248

Gnomad4 ASJ exome AF: 0.287

Gnomad4 EAS exome AF: 0.263

Gnomad4 SAS exome AF: 0.332

Gnomad4 FIN exome AF: 0.316

Gnomad4 NFE exome AF: 0.407

Gnomad4 OTH exome AF: 0.360

GnomAD4 genome AF: 0.289 AC: 44011 AN: 152130 Hom.: 7829 Cov.: 32 AF XY: 0.284 AC XY: 21089 AN XY: 74366

Gnomad4 AFR AF: 0.0798

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.311

Gnomad4 SAS AF: 0.312

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.338

Alfa AF: 0.381 Hom.: 22691

Bravo AF: 0.283

TwinsUK AF: 0.400 AC: 1484

ALSPAC AF: 0.419 AC: 1614

ESP6500AA AF: 0.0869 AC: 383

ESP6500EA AF: 0.404 AC: 3473

ExAC AF: 0.335 AC: 40656

Asia WGS AF: 0.253 AC: 877 AN: 3478

EpiCase AF: 0.410

EpiControl AF: 0.418

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	10
DANN	Benign	0.90
DEOGEN2	Benign	0.016	.;T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.64	T;T
MetaRNN	Benign	0.0030	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.7	.;L
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.14
Sift	Benign	0.19	T;T
Sift4G	Benign	0.54	T;T
Polyphen		0.14	B;B
Vest4		0.097
MPC		0.18
ClinPred		0.0086	T
GERP RS		2.6
Varity_R		0.057
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs11205303; hg19: chr1-149906413; COSMIC: COSV63804849; COSMIC: COSV63804849;