Genetic Variant TMEM120B:p.Leu59Phe (chr12-121743734-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001080825.2(TMEM120B):c.175C>T(p.Leu59Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,612,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

TMEM120B
NM_001080825.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.29

Publications

0 publications found

Variant links:

Genes affected

TMEM120B (HGNC:32008): (transmembrane protein 120B) Predicted to be involved in fat cell differentiation and protein heterooligomerization. Predicted to be integral component of membrane. Predicted to be active in nuclear inner membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM120B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0455561).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080825.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM120B	NM_001080825.2	MANE Select	c.175C>T	p.Leu59Phe	missense	Exon 2 of 12	NP_001074294.2	A0PK00

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM120B	ENST00000449592.7	TSL:1 MANE Select	c.175C>T	p.Leu59Phe	missense	Exon 2 of 12	ENSP00000404991.2	A0PK00
TMEM120B	ENST00000541467.1	TSL:5	c.112C>T	p.Leu38Phe	missense	Exon 1 of 10	ENSP00000442105.1	H0YG77
TMEM120B	ENST00000342607.10	TSL:2	n.175C>T		non_coding_transcript_exon	Exon 2 of 13	ENSP00000345152.6	A0PK00

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152008

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

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:

0.000478

GnomAD2 exomes

AF:

0.00000802

AC:

AN:

249224

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460640

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726612

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33450

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.00

AC:

AN:

86222

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53158

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5446

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111526

Other (OTH)

AF:

0.0000663

AC:

AN:

60308

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

AF:

0.0000395

AC:

AN:

152008

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74234

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41392

American (AMR)

AF:

0.000328

AC:

AN:

15226

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10578

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000165

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

Benign

0.070

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.64

CADD

Benign

5.7

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

Eigen

Benign

-0.96

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.12

M_CAP

Benign

0.0060

MetaRNN

Benign

0.046

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.6

PhyloP100

-1.3

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.63

REVEL

Benign

0.0080

Sift

Benign

0.088

Sift4G

Benign

0.067

Polyphen

0.015

Vest4

0.19

MutPred

0.40

Gain of methylation at K58 (P = 0.0801)

MVP

0.030

MPC

0.50

ClinPred

0.021

GERP RS

-1.5

PromoterAI

-0.020

Neutral

(source)

Varity_R

0.030

gMVP

0.081

Mutation Taster

=95/5

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over