Variant 11-87067726-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_022918.4(TMEM135):c.174C>G(p.Asp58Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000794 in 1,613,862 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0039 ( 9 hom., cov: 32)

Exomes 𝑓: 0.00047 ( 5 hom. )

Consequence

TMEM135
NM_022918.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.00900

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0067637563).

BP6

Variant 11-87067726-C-G is Benign according to our data. Variant chr11-87067726-C-G is described in ClinVar as [Benign]. Clinvar id is 787597.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TMEM135	NM_022918.4 linkuse as main transcript	c.174C>G	p.Asp58Glu	missense_variant	2/15	ENST00000305494.6
TMEM135	NM_001168724.2 linkuse as main transcript	c.174C>G	p.Asp58Glu	missense_variant	2/14
TMEM135	NR_033149.2 linkuse as main transcript	n.286C>G		non_coding_transcript_exon_variant	2/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM135	ENST00000305494.6 linkuse as main transcript	c.174C>G	p.Asp58Glu	missense_variant	2/15	1	NM_022918.4	P1	Q86UB9-1

Frequencies

GnomAD3 genomes

AF:

0.00395

AC:

601

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0139

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000917

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00108

AC:

271

AN:

251346

Hom.:

AF XY:

0.000839

AC XY:

114

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.0141

Gnomad AMR exome

AF:

0.000752

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000466

AC:

681

AN:

1461588

Hom.:

Cov.:

AF XY:

0.000388

AC XY:

282

AN XY:

727094

show subpopulations

Gnomad4 AFR exome

AF:

0.0137

Gnomad4 AMR exome

AF:

0.000827

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000116

Gnomad4 OTH exome

AF:

0.000894

GnomAD4 genome

AF:

0.00395

AC:

601

AN:

152274

Hom.:

Cov.:

AF XY:

0.00361

AC XY:

269

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0139

Gnomad4 AMR

AF:

0.000916

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000848

Hom.:

Bravo

AF:

0.00495

ESP6500AA

AF:

0.0159

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00131

AC:

159

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.94

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.64

T;T;T;T

MetaRNN

Benign

0.0068

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;.;.;L

MutationTaster

Benign

0.98

D;D;D;D;D

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.19

N;N;N;N

REVEL

Benign

0.036

Sift

Benign

0.34

T;T;T;T

Sift4G

Benign

0.71

T;T;T;T

Polyphen

0.0

B;.;.;B

Vest4

0.18

MutPred

0.30

Loss of ubiquitination at K54 (P = 0.0828);Loss of ubiquitination at K54 (P = 0.0828);Loss of ubiquitination at K54 (P = 0.0828);Loss of ubiquitination at K54 (P = 0.0828);

MVP

0.082

MPC

0.35

ClinPred

0.0079

GERP RS

-1.6

Varity_R

0.076

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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