dbSNP rs560118543: TMEM134:p.Pro160Leu (chr11-67464829-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_025124.4(TMEM134):c.479C>T(p.Pro160Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000054 in 1,610,310 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000053 ( 2 hom. )

Consequence

TMEM134
NM_025124.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.42

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16706017).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025124.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM134	NM_025124.4	MANE Select	c.479C>T	p.Pro160Leu	missense	Exon 6 of 7	NP_079400.1	Q9H6X4-1
TMEM134	NM_001078651.3		c.452C>T	p.Pro151Leu	missense	Exon 6 of 7	NP_001072119.1
TMEM134	NM_001078650.3		c.434C>T	p.Pro145Leu	missense	Exon 5 of 6	NP_001072118.1	Q9H6X4-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM134	ENST00000308022.7	TSL:2 MANE Select	c.479C>T	p.Pro160Leu	missense	Exon 6 of 7	ENSP00000312615.2	Q9H6X4-1
TMEM134	ENST00000393877.3	TSL:1	c.434C>T	p.Pro145Leu	missense	Exon 5 of 6	ENSP00000377455.3	Q9H6X4-2
TMEM134	ENST00000545682.5	TSL:1	n.*67C>T		non_coding_transcript_exon	Exon 6 of 7	ENSP00000438439.1	Q9H6X4-3

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000139

AC:

AN:

237988

AF XY:

0.000175

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000293

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000451

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000342

GnomAD4 exome

AF:

0.0000535

AC:

AN:

1458078

Hom.:

Cov.:

AF XY:

0.0000717

AC XY:

AN XY:

725242

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33404

American (AMR)

AF:

0.00

AC:

AN:

44654

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26106

East Asian (EAS)

AF:

0.000126

AC:

AN:

39672

South Asian (SAS)

AF:

0.000767

AC:

AN:

86090

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51798

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4530

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111646

Other (OTH)

AF:

0.0000997

AC:

AN:

60178

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41548

American (AMR)

AF:

0.00

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5178

South Asian (SAS)

AF:

0.000828

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67998

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.000150

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.65

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0045

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.21

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.046

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.69

PhyloP100

4.4

PrimateAI

Uncertain

0.75

PROVEAN

Benign

0.35

REVEL

Benign

0.15

Sift

Benign

0.16

Sift4G

Uncertain

0.052

Polyphen

1.0

Vest4

0.74

MutPred

0.51

Loss of sheet (P = 7e-04)

MVP

0.19

MPC

0.39

ClinPred

0.18

GERP RS

3.7

Varity_R

0.084

gMVP

0.90

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over