Variant 12-88153436-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_181783.4(TMTC3):c.335A>G(p.Lys112Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00223 in 1,613,684 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 68 hom. )

Consequence

TMTC3
NM_181783.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.38

Variant links:

Genes affected

TMTC3 (HGNC:26899): (transmembrane O-mannosyltransferase targeting cadherins 3) This gene encodes a protein that belongs to the transmembrane and tetratricopeptide repeat-containing protein family. [provided by RefSeq, May 2010]

TMTC3 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=0.002990514).

BP6

Variant 12-88153436-A-G is Benign according to our data. Variant chr12-88153436-A-G is described in ClinVar as [Benign]. Clinvar id is 723618.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMTC3	NM_181783.4 linkuse as main transcript	c.335A>G	p.Lys112Arg	missense_variant	3/14	ENST00000266712.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMTC3	ENST00000266712.11 linkuse as main transcript	c.335A>G	p.Lys112Arg	missense_variant	3/14	1	NM_181783.4	P1	Q6ZXV5-2
TMTC3	ENST00000547034.5 linkuse as main transcript	c.335A>G	p.Lys112Arg	missense_variant, NMD_transcript_variant	3/12	1
TMTC3	ENST00000549011.5 linkuse as main transcript	c.335A>G	p.Lys112Arg	missense_variant	3/4	4
TMTC3	ENST00000551088.1 linkuse as main transcript	c.190-852A>G		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00229

AC:

348

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.0438

Gnomad SAS

AF:

0.00517

Gnomad FIN

AF:

0.00236

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000794

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00436

AC:

1094

AN:

251148

Hom.:

AF XY:

0.00434

AC XY:

589

AN XY:

135764

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00298

Gnomad EAS exome

AF:

0.0441

Gnomad SAS exome

AF:

0.00255

Gnomad FIN exome

AF:

0.00329

Gnomad NFE exome

AF:

0.000687

Gnomad OTH exome

AF:

0.00229

GnomAD4 exome

AF:

0.00223

AC:

3253

AN:

1461378

Hom.:

Cov.:

AF XY:

0.00231

AC XY:

1676

AN XY:

727016

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000447

Gnomad4 ASJ exome

AF:

0.00184

Gnomad4 EAS exome

AF:

0.0532

Gnomad4 SAS exome

AF:

0.00312

Gnomad4 FIN exome

AF:

0.00294

Gnomad4 NFE exome

AF:

0.000440

Gnomad4 OTH exome

AF:

0.00247

GnomAD4 genome

AF:

0.00228

AC:

347

AN:

152306

Hom.:

Cov.:

AF XY:

0.00273

AC XY:

203

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00260

Gnomad4 EAS

AF:

0.0438

Gnomad4 SAS

AF:

0.00518

Gnomad4 FIN

AF:

0.00236

Gnomad4 NFE

AF:

0.000794

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00311

Hom.:

Bravo

AF:

0.00248

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.00455

AC:

552

Asia WGS

AF:

0.0240

AC:

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.000652

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

TMTC3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 27, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 10, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.27

CADD

Benign

3.7

DANN

Benign

0.36

DEOGEN2

Benign

0.0090

T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.68

T;T

MetaRNN

Benign

0.0030

T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

-0.63

.;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.23

PROVEAN

Benign

0.33

N;N

REVEL

Benign

0.20

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

.;B

Vest4

0.090

MVP

0.71

MPC

0.26

ClinPred

0.0032

GERP RS

-2.3

gMVP

0.35

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