Variant 11-87309619-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_022918.4(TMEM135):c.883A>G(p.Lys295Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00019 in 1,613,866 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000091 ( 0 hom. )

Consequence

TMEM135
NM_022918.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.13

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.016928613).

BP6

Variant 11-87309619-A-G is Benign according to our data. Variant chr11-87309619-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3053841.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM135	NM_022918.4 linkuse as main transcript	c.883A>G	p.Lys295Glu	missense_variant	10/15	ENST00000305494.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM135	ENST00000305494.6 linkuse as main transcript	c.883A>G	p.Lys295Glu	missense_variant	10/15	1	NM_022918.4	P1	Q86UB9-1
TMEM135	ENST00000340353.11 linkuse as main transcript	c.817A>G	p.Lys273Glu	missense_variant	9/14	1			Q86UB9-2
TMEM135	ENST00000532959.5 linkuse as main transcript	c.496A>G	p.Lys166Glu	missense_variant	7/12	2

Frequencies

GnomAD3 genomes

AF:

0.00113

AC:

172

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00400

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000259

AC:

AN:

251086

Hom.:

AF XY:

0.000184

AC XY:

AN XY:

135718

show subpopulations

Gnomad AFR exome

AF:

0.00358

Gnomad AMR exome

AF:

0.000116

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:

0.00

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000910

AC:

133

AN:

1461556

Hom.:

Cov.:

AF XY:

0.0000825

AC XY:

AN XY:

727094

show subpopulations

Gnomad4 AFR exome

AF:

0.00320

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.00114

AC:

174

AN:

152310

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00404

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000231

Hom.:

Bravo

AF:

0.00140

ESP6500AA

AF:

0.00545

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000379

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

TMEM135-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 30, 2023

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

0.33

BayesDel_addAF

Benign

-0.084

BayesDel_noAF

Uncertain

0.11

Cadd

Pathogenic

Dann

Uncertain

1.0

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Benign

0.028

MetaRNN

Benign

0.017

T;T;T

MetaSVM

Benign

-0.75

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-2.6

D;D;D

REVEL

Uncertain

0.33

Sift

Uncertain

0.0050

D;D;D

Sift4G

Benign

0.17

T;D;T

Polyphen

0.99

D;.;D

Vest4

0.76

MVP

0.37

MPC

0.98

ClinPred

0.049

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.63

gMVP

0.78

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