Variant 11-87305959-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The ENST00000305494.6(TMEM135):c.722G>A(p.Arg241Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00105 in 1,603,436 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 4 hom. )

Consequence

TMEM135
ENST00000305494.6 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 7.84

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01532644).

BP6

Variant 11-87305959-G-A is Benign according to our data. Variant chr11-87305959-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3040712.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM135	NM_022918.4 linkuse as main transcript	c.722G>A	p.Arg241Lys	missense_variant	9/15	ENST00000305494.6	NP_075069.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM135	ENST00000305494.6 linkuse as main transcript	c.722G>A	p.Arg241Lys	missense_variant	9/15	1	NM_022918.4	ENSP00000306344	P1	Q86UB9-1
TMEM135	ENST00000340353.11 linkuse as main transcript	c.656G>A	p.Arg219Lys	missense_variant	8/14	1		ENSP00000345513		Q86UB9-2
TMEM135	ENST00000532959.5 linkuse as main transcript	c.335G>A	p.Arg112Lys	missense_variant	6/12	2		ENSP00000436179

Frequencies

GnomAD3 genomes

AF:

0.00123

AC:

186

AN:

151748

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000387

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00256

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.00153

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00139

AC:

348

AN:

250008

Hom.:

AF XY:

0.00138

AC XY:

187

AN XY:

135162

show subpopulations

Gnomad AFR exome

AF:

0.000310

Gnomad AMR exome

AF:

0.00230

Gnomad ASJ exome

AF:

0.00428

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00125

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00149

Gnomad OTH exome

AF:

0.00230

GnomAD4 exome

AF:

0.00103

AC:

1500

AN:

1451570

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

758

AN XY:

721834

show subpopulations

Gnomad4 AFR exome

AF:

0.000510

Gnomad4 AMR exome

AF:

0.00205

Gnomad4 ASJ exome

AF:

0.00395

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00129

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000979

Gnomad4 OTH exome

AF:

0.00129

GnomAD4 genome

AF:

0.00122

AC:

186

AN:

151866

Hom.:

Cov.:

AF XY:

0.00115

AC XY:

AN XY:

74194

show subpopulations

Gnomad4 AFR

AF:

0.000386

Gnomad4 AMR

AF:

0.00256

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00153

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00141

Hom.:

Bravo

AF:

0.00116

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00187

AC:

ExAC

AF:

0.00128

AC:

155

Asia WGS

AF:

0.000580

AC:

AN:

3462

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TMEM135-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 15, 2022

This variant is classified as likely 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

0.13

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0030

.;.;T

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.86

D;D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.015

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

.;.;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.10

N;N;N

REVEL

Benign

0.13

Sift

Benign

0.83

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.96

D;.;D

Vest4

0.47

MVP

0.36

MPC

0.39

ClinPred

0.21

GERP RS

5.6

Varity_R

0.24

gMVP

0.59

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