Variant 11-87321245-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_022918.4(TMEM135):c.1289G>C(p.Gly430Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0294 in 1,613,404 control chromosomes in the GnomAD database, including 1,433 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 (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.029 ( 135 hom., cov: 32)

Exomes 𝑓: 0.030 ( 1298 hom. )

Consequence

TMEM135
NM_022918.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.61

Variant links:

Genes affected

TMEM135 (HGNC:26167): (transmembrane protein 135) Predicted to be involved in peroxisome organization. Predicted to act upstream of or within response to cold and response to food. Predicted to be located in mitochondrion and peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

TMEM135 links:

TMEM135 (HGNC:):

TMEM135 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012643337).

BP6

Variant 11-87321245-G-C is Benign according to our data. Variant chr11-87321245-G-C is described in ClinVar as [Benign]. Clinvar id is 3056487.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM135	NM_022918.4 linkuse as main transcript	c.1289G>C	p.Gly430Ala	missense_variant	15/15	ENST00000305494.6	NP_075069.3	Q86UB9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM135	ENST00000305494.6 linkuse as main transcript	c.1289G>C	p.Gly430Ala	missense_variant	15/15	1	NM_022918.4	ENSP00000306344.5		Q86UB9-1

Frequencies

GnomAD3 genomes

AF:

0.0287

AC:

4363

AN:

151976

Hom.:

135

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0233

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.0230

Gnomad ASJ

AF:

0.0314

Gnomad EAS

AF:

0.165

Gnomad SAS

AF:

0.0819

Gnomad FIN

AF:

0.0101

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0219

Gnomad OTH

AF:

0.0268

GnomAD3 exomes

AF:

0.0411

AC:

10322

AN:

251126

Hom.:

459

AF XY:

0.0430

AC XY:

5839

AN XY:

135740

show subpopulations

Gnomad AFR exome

AF:

0.0219

Gnomad AMR exome

AF:

0.0227

Gnomad ASJ exome

AF:

0.0368

Gnomad EAS exome

AF:

0.176

Gnomad SAS exome

AF:

0.0830

Gnomad FIN exome

AF:

0.00855

Gnomad NFE exome

AF:

0.0234

Gnomad OTH exome

AF:

0.0312

GnomAD4 exome

AF:

0.0295

AC:

43123

AN:

1461312

Hom.:

1298

Cov.:

AF XY:

0.0313

AC XY:

22728

AN XY:

726982

show subpopulations

Gnomad4 AFR exome

AF:

0.0234

Gnomad4 AMR exome

AF:

0.0226

Gnomad4 ASJ exome

AF:

0.0344

Gnomad4 EAS exome

AF:

0.166

Gnomad4 SAS exome

AF:

0.0814

Gnomad4 FIN exome

AF:

0.00953

Gnomad4 NFE exome

AF:

0.0214

Gnomad4 OTH exome

AF:

0.0358

GnomAD4 genome

AF:

0.0287

AC:

4372

AN:

152092

Hom.:

135

Cov.:

AF XY:

0.0303

AC XY:

2251

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0233

Gnomad4 AMR

AF:

0.0230

Gnomad4 ASJ

AF:

0.0314

Gnomad4 EAS

AF:

0.166

Gnomad4 SAS

AF:

0.0824

Gnomad4 FIN

AF:

0.0101

Gnomad4 NFE

AF:

0.0219

Gnomad4 OTH

AF:

0.0265

Alfa

AF:

0.0286

Hom.:

Bravo

AF:

0.0307

TwinsUK

AF:

0.0237

AC:

ALSPAC

AF:

0.0213

AC:

ESP6500AA

AF:

0.0202

AC:

ESP6500EA

AF:

0.0241

AC:

207

ExAC

AF:

0.0421

AC:

5117

Asia WGS

AF:

0.124

AC:

431

AN:

3476

EpiCase

AF:

0.0252

EpiControl

AF:

0.0263

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TMEM135-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 14, 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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.68

DEOGEN2

Benign

0.0044

.;.;T

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.31

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.92

D;D;D

MetaRNN

Benign

0.0013

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

.;.;L

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.48

N;N;N

REVEL

Benign

0.045

Sift

Benign

0.25

T;T;T

Sift4G

Benign

0.20

T;T;T

Polyphen

0.0020

B;.;B

Vest4

0.13

MPC

0.41

ClinPred

0.0054

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.037

gMVP

0.41

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