Variant 12-94582053-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000261226.9(TMCC3):c.564G>A(p.Met188Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00674 in 1,614,188 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0054 ( 4 hom., cov: 31)

Exomes 𝑓: 0.0069 ( 42 hom. )

Consequence

TMCC3
ENST00000261226.9 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.35

Variant links:

Genes affected

TMCC3 (HGNC:29199): (transmembrane and coiled-coil domain family 3) Enables 14-3-3 protein binding activity and identical protein binding activity. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

TMCC3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0073962808).

BP6

Variant 12-94582053-C-T is Benign according to our data. Variant chr12-94582053-C-T is described in ClinVar as [Benign]. Clinvar id is 783669.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMCC3	NM_020698.4 linkuse as main transcript	c.564G>A	p.Met188Ile	missense_variant	2/4	ENST00000261226.9	NP_065749.3	Q9ULS5
TMCC3	NM_001301036.2 linkuse as main transcript	c.471G>A	p.Met157Ile	missense_variant	2/4		NP_001287965.1	Q9ULS5G3V207

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMCC3	ENST00000261226.9 linkuse as main transcript	c.564G>A	p.Met188Ile	missense_variant	2/4	1	NM_020698.4	ENSP00000261226.4		Q9ULS5
TMCC3	ENST00000551457.1 linkuse as main transcript	c.471G>A	p.Met157Ile	missense_variant	2/4	1		ENSP00000449888.1		G3V207

Frequencies

GnomAD3 genomes

AF:

0.00543

AC:

826

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00661

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00857

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00813

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00502

AC:

1263

AN:

251376

Hom.:

AF XY:

0.00490

AC XY:

666

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.00460

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000555

Gnomad FIN exome

AF:

0.00776

Gnomad NFE exome

AF:

0.00746

Gnomad OTH exome

AF:

0.00652

GnomAD4 exome

AF:

0.00688

AC:

10059

AN:

1461856

Hom.:

Cov.:

AF XY:

0.00677

AC XY:

4924

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.00492

Gnomad4 ASJ exome

AF:

0.00157

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000835

Gnomad4 FIN exome

AF:

0.00743

Gnomad4 NFE exome

AF:

0.00801

Gnomad4 OTH exome

AF:

0.00641

GnomAD4 genome

AF:

0.00543

AC:

827

AN:

152332

Hom.:

Cov.:

AF XY:

0.00557

AC XY:

415

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00135

Gnomad4 AMR

AF:

0.00660

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00857

Gnomad4 NFE

AF:

0.00814

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00702

Hom.:

Bravo

AF:

0.00491

TwinsUK

AF:

0.00728

AC:

ALSPAC

AF:

0.00597

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00733

AC:

ExAC

AF:

0.00474

AC:

575

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00627

EpiControl

AF:

0.00670

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.0043

T;.

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.093

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.0046

MetaRNN

Benign

0.0074

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.080

N;.

MutationTaster

Benign

0.87

D;D

PrimateAI

Uncertain

0.50

PROVEAN

Benign

0.13

N;N

REVEL

Benign

0.13

Sift

Benign

0.77

T;T

Sift4G

Benign

0.93

T;T

Polyphen

0.020

B;.

Vest4

0.33

MutPred

0.32

Loss of disorder (P = 0.0619);.;

MVP

0.076

MPC

0.33

ClinPred

0.029

GERP RS

5.7

Varity_R

0.30

gMVP

0.15

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