Variant 11-87318221-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.1162A>G(p.Ile388Val) variant causes a missense change. The variant allele was found at a frequency of 0.000241 in 1,611,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

TMEM135
NM_022918.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.09

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=0.010766566).

BP6

Variant 11-87318221-A-G is Benign according to our data. Variant chr11-87318221-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3049524.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.1162A>G	p.Ile388Val	missense_variant	13/15	ENST00000305494.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM135	ENST00000305494.6 linkuse as main transcript	c.1162A>G	p.Ile388Val	missense_variant	13/15	1	NM_022918.4	P1	Q86UB9-1
TMEM135	ENST00000340353.11 linkuse as main transcript	c.1096A>G	p.Ile366Val	missense_variant	12/14	1			Q86UB9-2
TMEM135	ENST00000531643.1 linkuse as main transcript	n.87A>G		non_coding_transcript_exon_variant	1/3	1
TMEM135	ENST00000532959.5 linkuse as main transcript	c.775A>G	p.Ile259Val	missense_variant	10/12	2

Frequencies

GnomAD3 genomes

AF:

0.00123

AC:

187

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00437

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

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:

0.0000147

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000353

AC:

AN:

249248

Hom.:

AF XY:

0.000252

AC XY:

AN XY:

134768

show subpopulations

Gnomad AFR exome

AF:

0.00505

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000139

AC:

203

AN:

1459278

Hom.:

Cov.:

AF XY:

0.000106

AC XY:

AN XY:

726076

show subpopulations

Gnomad4 AFR exome

AF:

0.00538

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000990

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.00122

AC:

186

AN:

152242

Hom.:

Cov.:

AF XY:

0.00130

AC XY:

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.00433

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000196

Hom.:

Bravo

AF:

0.00151

ESP6500AA

AF:

0.00568

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000445

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

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 16, 2019

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

0.070

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.25

Cadd

Benign

Dann

Benign

0.80

Eigen

Benign

0.011

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.85

T;T;T

M_CAP

Benign

0.0049

MetaRNN

Benign

0.011

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.060

N;N;N

REVEL

Benign

0.18

Sift

Benign

0.62

T;T;T

Sift4G

Benign

0.13

T;T;T

Polyphen

0.026

B;.;B

Vest4

0.37

MVP

0.43

MPC

0.31

ClinPred

0.050

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.47

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