Genetic Variant TMEM134:p.Phe187Leu (chr11-67464641-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_025124.4(TMEM134):c.561C>G(p.Phe187Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000285 in 1,401,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

TMEM134
NM_025124.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.634

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38576245).

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.561C>G	p.Phe187Leu	missense	Exon 7 of 7	NP_079400.1	Q9H6X4-1
TMEM134	NM_001078651.3		c.534C>G	p.Phe178Leu	missense	Exon 7 of 7	NP_001072119.1
TMEM134	NM_001078650.3		c.516C>G	p.Phe172Leu	missense	Exon 6 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.561C>G	p.Phe187Leu	missense	Exon 7 of 7	ENSP00000312615.2	Q9H6X4-1
TMEM134	ENST00000393877.3	TSL:1	c.516C>G	p.Phe172Leu	missense	Exon 6 of 6	ENSP00000377455.3	Q9H6X4-2
TMEM134	ENST00000545682.5	TSL:1	n.*149C>G		non_coding_transcript_exon	Exon 7 of 7	ENSP00000438439.1	Q9H6X4-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

156728

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000285

AC:

AN:

1401056

Hom.:

Cov.:

AF XY:

0.00000434

AC XY:

AN XY:

691232

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31710

American (AMR)

AF:

0.00

AC:

AN:

35950

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25202

East Asian (EAS)

AF:

0.00

AC:

AN:

35958

South Asian (SAS)

AF:

0.0000378

AC:

AN:

79374

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49296

Middle Eastern (MID)

AF:

0.000176

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1079814

Other (OTH)

AF:

0.00

AC:

AN:

58054

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

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Uncertain

0.021

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Benign

0.12

Eigen_PC

Benign

0.17

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.83

M_CAP

Benign

0.050

MetaRNN

Benign

0.39

MetaSVM

Benign

-0.58

MutationAssessor

Benign

1.9

PhyloP100

0.63

PrimateAI

Uncertain

0.68

PROVEAN

Pathogenic

-4.8

REVEL

Benign

0.20

Sift

Benign

0.083

Sift4G

Benign

0.29

Polyphen

0.99

Vest4

0.45

MutPred

0.81

Gain of sheet (P = 0.1451)

MVP

0.055

MPC

0.45

ClinPred

0.95

GERP RS

4.1

Varity_R

0.34

gMVP

0.89

Mutation Taster

=60/40

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over