dbSNP rs748087421: TMEM134:p.Leu139Pro (chr11-67465091-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_025124.4(TMEM134):c.416T>C(p.Leu139Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000946 in 1,586,250 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000098 ( 0 hom. )

Consequence

TMEM134
NM_025124.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.16

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: Uncertain_significance. The variant received 0 ACMG points.

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.416T>C	p.Leu139Pro	missense	Exon 5 of 7	NP_079400.1	Q9H6X4-1
TMEM134	NM_001078651.3		c.389T>C	p.Leu130Pro	missense	Exon 5 of 7	NP_001072119.1
TMEM134	NM_001078650.3		c.407-235T>C		intron	N/A	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.416T>C	p.Leu139Pro	missense	Exon 5 of 7	ENSP00000312615.2	Q9H6X4-1
TMEM134	ENST00000393877.3	TSL:1	c.407-235T>C		intron	N/A	ENSP00000377455.3	Q9H6X4-2
TMEM134	ENST00000545682.5	TSL:1	n.*4T>C		non_coding_transcript_exon	Exon 5 of 7	ENSP00000438439.1	Q9H6X4-3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000493

AC:

AN:

202658

AF XY:

0.0000445

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000334

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000976

AC:

AN:

1434088

Hom.:

Cov.:

AF XY:

0.0000112

AC XY:

AN XY:

712574

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32852

American (AMR)

AF:

0.000340

AC:

AN:

41202

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24944

East Asian (EAS)

AF:

0.00

AC:

AN:

39214

South Asian (SAS)

AF:

0.00

AC:

AN:

83368

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45384

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5582

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1102278

Other (OTH)

AF:

0.00

AC:

AN:

59264

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

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:

0.00000657

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41442

American (AMR)

AF:

0.0000655

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.0000189

ExAC

AF:

0.0000417

AC:

ClinVar

ClinVar submissions

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

0.68

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.66

M_CAP

Benign

0.019

MetaRNN

Uncertain

0.66

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.67

PhyloP100

1.2

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-3.1

REVEL

Uncertain

0.42

Sift

Benign

0.041

Sift4G

Benign

0.22

Polyphen

1.0

Vest4

0.79

MutPred

0.67

Loss of sheet (P = 0.0126)

MVP

0.53

MPC

0.53

ClinPred

0.52

GERP RS

4.2

Varity_R

0.72

gMVP

0.81

Mutation Taster

=72/28

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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