Variant 12-121748420-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001080825.2(TMEM120B):c.283G>A(p.Ala95Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000011 in 1,457,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

TMEM120B
NM_001080825.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.47

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3510244).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM120B	NM_001080825.2 linkuse as main transcript	c.283G>A	p.Ala95Thr	missense_variant	3/12	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.283G>A	p.Ala95Thr	missense_variant	3/12	1	NM_001080825.2	ENSP00000404991.2	A0PK00
TMEM120B	ENST00000541467.1 linkuse as main transcript	c.220G>A	p.Ala74Thr	missense_variant	2/10	5		ENSP00000442105.1	H0YG77
TMEM120B	ENST00000342607.10 linkuse as main transcript	n.283G>A		non_coding_transcript_exon_variant	3/13	2		ENSP00000345152.6	A0PK00

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000163

AC:

AN:

246050

Hom.:

AF XY:

0.00000747

AC XY:

AN XY:

133842

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000588

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000180

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1457506

Hom.:

Cov.:

AF XY:

0.00000690

AC XY:

AN XY:

724926

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000451

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000901

Gnomad4 OTH exome

AF:

0.0000665

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000378

ExAC

AF:

0.00000827

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

Dec 15, 2023

The c.283G>A (p.A95T) alteration is located in exon 3 (coding exon 3) of the TMEM120B gene. This alteration results from a G to A substitution at nucleotide position 283, causing the alanine (A) at amino acid position 95 to be replaced by a threonine (T). 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

0.17

BayesDel_addAF

Benign

0.0070

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.021

T;.

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.35

T;T

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.6

M;.

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.17

Sift

Benign

0.097

T;T

Sift4G

Benign

0.37

T;T

Polyphen

0.33

B;.

Vest4

0.44

MutPred

0.45

Gain of catalytic residue at Y96 (P = 0.0424);.;

MVP

0.30

MPC

0.83

ClinPred

0.41

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.24

gMVP

0.40

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