Variant 12-121743672-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001080825.2(TMEM120B):c.113C>T(p.Ala38Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000219 in 1,461,470 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

TMEM120B
NM_001080825.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.906

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09401536).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM120B	NM_001080825.2 linkuse as main transcript	c.113C>T	p.Ala38Val	missense_variant	2/12	ENST00000449592.7	NP_001074294.2	A0PK00

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TMEM120B	ENST00000449592.7 linkuse as main transcript	c.113C>T	p.Ala38Val	missense_variant	2/12	1	NM_001080825.2	ENSP00000404991.2	A0PK00
TMEM120B	ENST00000541467.1 linkuse as main transcript	c.50C>T	p.Ala17Val	missense_variant	1/10	5		ENSP00000442105.1	H0YG77
TMEM120B	ENST00000342607.10 linkuse as main transcript	n.113C>T		non_coding_transcript_exon_variant	2/13	2		ENSP00000345152.6	A0PK00

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000241

AC:

AN:

249286

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

135318

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000219

AC:

AN:

1461470

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

727032

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000248

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 26, 2024

The c.113C>T (p.A38V) alteration is located in exon 2 (coding exon 2) of the TMEM120B gene. This alteration results from a C to T substitution at nucleotide position 113, causing the alanine (A) at amino acid position 38 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.038

T;.

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.59

T;T

M_CAP

Benign

0.0040

MetaRNN

Benign

0.094

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;.

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.042

Sift

Benign

0.14

T;T

Sift4G

Benign

0.17

T;T

Polyphen

0.011

B;.

Vest4

0.20

MutPred

0.43

Gain of catalytic residue at L42 (P = 0.015);.;

MVP

0.081

MPC

0.49

ClinPred

0.098

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.045

gMVP

0.11

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

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