dbSNP rs145260557: MTMR12:p.Arg556Leu (chr5-32233780-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001040446.3(MTMR12):c.1667G>T(p.Arg556Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R556C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

MTMR12
NM_001040446.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.564

Variant links:

Genes affected

MTMR12 (HGNC:18191): (myotubularin related protein 12) Phosphatidylinositide 3-kinase-derived membrane-anchored phosphatidylinositides, such as phosphatidylinositol 3-phosphate (PtdIns(3)P), regulate diverse cellular processes. The protein encoded by this gene functions as an adaptor subunit in a complex with an active PtdIns(3)P 3-phosphatase. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2014]

MTMR12 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35707527).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTMR12	NM_001040446.3 link	c.1667G>T	p.Arg556Leu	missense_variant	Exon 15 of 16	ENST00000382142.8	NP_001035536.1	Q9C0I1-1
MTMR12	NM_001294343.2 link	c.1512+1182G>T		intron_variant	Intron 14 of 14		NP_001281272.1	Q9C0I1-2
MTMR12	NM_001294344.2 link	c.1345-3433G>T		intron_variant	Intron 13 of 13		NP_001281273.1	Q9C0I1-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MTMR12	ENST00000382142.8 link	c.1667G>T	p.Arg556Leu	missense_variant	Exon 15 of 16	1	NM_001040446.3	ENSP00000371577.3	Q9C0I1-1
MTMR12	ENST00000280285.9 link	c.1512+1182G>T		intron_variant	Intron 14 of 14	1		ENSP00000280285.5	Q9C0I1-2
MTMR12	ENST00000264934.5 link	c.1345-3433G>T		intron_variant	Intron 13 of 13	2		ENSP00000264934.5	Q9C0I1-3
MTMR12	ENST00000510216.1 link	n.114G>T		non_coding_transcript_exon_variant	Exon 1 of 3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251474

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Uncertain

0.065

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.018

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.47

LIST_S2

Uncertain

0.91

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.36

MetaSVM

Uncertain

-0.28

MutationAssessor

Benign

2.0

PrimateAI

Benign

0.21

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.33

Sift

Uncertain

0.018

Sift4G

Uncertain

0.037

Polyphen

0.36

Vest4

0.65

MutPred

0.35

Loss of solvent accessibility (P = 0.0238);

MVP

0.37

MPC

0.76

ClinPred

0.12

GERP RS

-1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.48

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over