Variant 11-67467580-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4BP6_ModerateBS2

The NM_025124.4(TMEM134):c.250C>T(p.Arg84Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00538 in 1,613,978 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0046 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0055 ( 30 hom. )

Consequence

TMEM134
NM_025124.4 stop_gained

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.81

Variant links:

Genes affected

TMEM134 (HGNC:26142): (transmembrane protein 134) Located in cytosol and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TMEM134 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM4

Stoplost variant in NM_025124.4 Downstream stopcodon found after 3 codons.

BP6

Variant 11-67467580-G-A is Benign according to our data. Variant chr11-67467580-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2642020.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM134	NM_025124.4 linkuse as main transcript	c.250C>T	p.Arg84Ter	stop_gained	3/7	ENST00000308022.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM134	ENST00000308022.7 linkuse as main transcript	c.250C>T	p.Arg84Ter	stop_gained	3/7	2	NM_025124.4	P1	Q9H6X4-1

Frequencies

GnomAD3 genomes

AF:

0.00463

AC:

704

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00471

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00452

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00741

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00427

AC:

1073

AN:

251010

Hom.:

AF XY:

0.00440

AC XY:

598

AN XY:

135792

show subpopulations

Gnomad AFR exome

AF:

0.000802

Gnomad AMR exome

AF:

0.00147

Gnomad ASJ exome

AF:

0.00139

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00157

Gnomad FIN exome

AF:

0.00454

Gnomad NFE exome

AF:

0.00728

Gnomad OTH exome

AF:

0.00375

GnomAD4 exome

AF:

0.00546

AC:

7974

AN:

1461668

Hom.:

Cov.:

AF XY:

0.00543

AC XY:

3950

AN XY:

727128

show subpopulations

Gnomad4 AFR exome

AF:

0.000657

Gnomad4 AMR exome

AF:

0.00174

Gnomad4 ASJ exome

AF:

0.00130

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00161

Gnomad4 FIN exome

AF:

0.00649

Gnomad4 NFE exome

AF:

0.00635

Gnomad4 OTH exome

AF:

0.00460

GnomAD4 genome

AF:

0.00463

AC:

705

AN:

152310

Hom.:

Cov.:

AF XY:

0.00396

AC XY:

295

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.00471

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.00452

Gnomad4 NFE

AF:

0.00741

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00605

Hom.:

Bravo

AF:

0.00430

TwinsUK

AF:

0.00566

AC:

ALSPAC

AF:

0.00752

AC:

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00605

AC:

ExAC

AF:

0.00462

AC:

561

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00627

EpiControl

AF:

0.00569

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

TMEM134: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.036

BayesDel_noAF

Pathogenic

0.19

Cadd

Pathogenic

Dann

Uncertain

0.98

Eigen

Benign

0.11

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.17

MutationTaster

Benign

1.0

A;A;N

Vest4

0.14

GERP RS

2.6

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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