rs11205303

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 96 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145862.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTMR11	NM_001145862.2	MANE Select	c.475A>G	p.Met159Val	missense	Exon 6 of 17	NP_001139334.1
	MTMR11	NM_181873.3		c.259A>G	p.Met87Val	missense	Exon 5 of 17	NP_870988.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTMR11	ENST00000439741.4	TSL:2 MANE Select	c.475A>G	p.Met159Val	missense	Exon 6 of 17	ENSP00000391668.2
	MTMR11	ENST00000466496.5	TSL:1	n.402A>G		non_coding_transcript_exon	Exon 5 of 10
	MTMR11	ENST00000482343.5	TSL:1	n.662A>G		non_coding_transcript_exon	Exon 6 of 9

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

GnomAD2 exomes AF: 0.333 AC: 83545 AN: 251124 AF XY: 0.344

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 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

African (AFR) AF: 0.0649 AC: 2173 AN: 33478

American (AMR) AF: 0.248 AC: 11082 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 7502 AN: 26128

East Asian (EAS) AF: 0.263 AC: 10454 AN: 39694

South Asian (SAS) AF: 0.332 AC: 28625 AN: 86220

European-Finnish (FIN) AF: 0.316 AC: 16887 AN: 53412

Middle Eastern (MID) AF: 0.386 AC: 2226 AN: 5768

European-Non Finnish (NFE) AF: 0.407 AC: 452525 AN: 1111146

Other (OTH) AF: 0.360 AC: 21715 AN: 60382

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

African (AFR) AF: 0.0798 AC: 3316 AN: 41536

American (AMR) AF: 0.289 AC: 4418 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 995 AN: 3472

East Asian (EAS) AF: 0.311 AC: 1612 AN: 5176

South Asian (SAS) AF: 0.312 AC: 1505 AN: 4820

European-Finnish (FIN) AF: 0.306 AC: 3238 AN: 10568

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.407 AC: 27642 AN: 67966

Other (OTH) AF: 0.338 AC: 713 AN: 2108

Alfa AF: 0.365 Hom.: 46329

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 v4.9

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
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.56
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.14
Sift	Benign	0.19	T
Sift4G	Benign	0.54	T
Polyphen		0.14	B
Vest4		0.097
MPC		0.18
ClinPred		0.0086	T
GERP RS		2.6
Varity_R		0.057
gMVP		0.53
Mutation Taster		=95/5	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11205303; hg19: chr1-149906413; COSMIC: COSV63804849; COSMIC: COSV63804849;