5-32230196-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001040446.3(MTMR12):c.1826T>C(p.Phe609Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,614,214 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0054 ( 12 hom., cov: 32)

Exomes 𝑓: 0.00057 ( 8 hom. )

Consequence

MTMR12
NM_001040446.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.12

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034379363).

BP6

Variant 5-32230196-A-G is Benign according to our data. Variant chr5-32230196-A-G is described in ClinVar as [Benign]. Clinvar id is 791090.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00536 (816/152320) while in subpopulation AFR AF= 0.0188 (783/41572). AF 95% confidence interval is 0.0177. There are 12 homozygotes in gnomad4. There are 402 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTMR12	NM_001040446.3 link	c.1826T>C	p.Phe609Ser	missense_variant	Exon 16 of 16	ENST00000382142.8	NP_001035536.1	Q9C0I1-1
MTMR12	NM_001294343.2 link	c.1664T>C	p.Phe555Ser	missense_variant	Exon 15 of 15		NP_001281272.1	Q9C0I1-2
MTMR12	NM_001294344.2 link	c.1496T>C	p.Phe499Ser	missense_variant	Exon 14 of 14		NP_001281273.1	Q9C0I1-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MTMR12	ENST00000382142.8 link	c.1826T>C	p.Phe609Ser	missense_variant	Exon 16 of 16	1	NM_001040446.3	ENSP00000371577.3	Q9C0I1-1
MTMR12	ENST00000280285.9 link	c.1664T>C	p.Phe555Ser	missense_variant	Exon 15 of 15	1		ENSP00000280285.5	Q9C0I1-2
MTMR12	ENST00000264934.5 link	c.1496T>C	p.Phe499Ser	missense_variant	Exon 14 of 14	2		ENSP00000264934.5	Q9C0I1-3
MTMR12	ENST00000510216.1 link	n.333T>C		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.00534

AC:

813

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0188

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00130

AC:

327

AN:

251476

Hom.:

AF XY:

0.000942

AC XY:

128

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.0181

Gnomad AMR exome

AF:

0.000694

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000574

AC:

839

AN:

1461894

Hom.:

Cov.:

AF XY:

0.000523

AC XY:

380

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0204

Gnomad4 AMR exome

AF:

0.000961

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.00142

GnomAD4 genome

AF:

0.00536

AC:

816

AN:

152320

Hom.:

Cov.:

AF XY:

0.00540

AC XY:

402

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0188

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00105

Hom.:

Bravo

AF:

0.00615

ESP6500AA

AF:

0.0157

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00153

AC:

186

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.75

DEOGEN2

Benign

0.0084

.;T;.

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.65

T;T;T

MetaRNN

Benign

0.0034

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.73

.;N;.

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.7

N;N;N

REVEL

Benign

0.050

Sift

Benign

0.49

T;T;T

Sift4G

Benign

0.60

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.18

MVP

0.043

MPC

0.85

ClinPred

0.0030

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.058

gMVP

0.54

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over