Variant 7-75989186-G-A 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_031925.3(TMEM120A):c.356C>T(p.Thr119Met) variant causes a missense change. The variant allele was found at a frequency of 0.0001 in 1,562,362 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000094 ( 0 hom., cov: 24)

Exomes 𝑓: 0.00010 ( 1 hom. )

Consequence

TMEM120A
NM_031925.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.09

Variant links:

Genes affected

TMEM120A (HGNC:21697): (transmembrane protein 120A) Predicted to enable ion channel activity. Involved in fat cell differentiation; protein heterooligomerization; and protein homooligomerization. Predicted to be located in plasma membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM120A links:

Genome browser will be placed here

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=0.07629827).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM120A	NM_031925.3 linkuse as main transcript	c.356C>T	p.Thr119Met	missense_variant	4/12	ENST00000493111.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM120A	ENST00000493111.7 linkuse as main transcript	c.356C>T	p.Thr119Met	missense_variant	4/12	1	NM_031925.3	P1	Q9BXJ8-1

Frequencies

GnomAD3 genomes

AF:

0.0000941

AC:

AN:

148704

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000754

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000201

Gnomad SAS

AF:

0.000645

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000104

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000127

AC:

AN:

181422

Hom.:

AF XY:

0.000165

AC XY:

AN XY:

97056

show subpopulations

Gnomad AFR exome

AF:

0.000203

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000152

Gnomad SAS exome

AF:

0.000708

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000130

Gnomad OTH exome

AF:

0.000209

GnomAD4 exome

AF:

0.000101

AC:

143

AN:

1413556

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

698808

show subpopulations

Gnomad4 AFR exome

AF:

0.000248

Gnomad4 AMR exome

AF:

0.0000265

Gnomad4 ASJ exome

AF:

0.0000395

Gnomad4 EAS exome

AF:

0.000242

Gnomad4 SAS exome

AF:

0.000573

Gnomad4 FIN exome

AF:

0.0000204

Gnomad4 NFE exome

AF:

0.0000643

Gnomad4 OTH exome

AF:

0.000119

GnomAD4 genome

AF:

0.0000941

AC:

AN:

148806

Hom.:

Cov.:

AF XY:

0.0000966

AC XY:

AN XY:

72500

show subpopulations

Gnomad4 AFR

AF:

0.0000752

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000201

Gnomad4 SAS

AF:

0.000646

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000104

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000959

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.000154

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 08, 2021

The c.356C>T (p.T119M) alteration is located in exon 4 (coding exon 4) of the TMEM120A gene. This alteration results from a C to T substitution at nucleotide position 356, causing the threonine (T) at amino acid position 119 to be replaced by a methionine (M). 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

Uncertain

0.48

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Pathogenic

0.28

CADD

Pathogenic

DANN

Benign

0.93

DEOGEN2

Benign

0.19

T;T;.

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

1.0

D;.;D

MetaRNN

Benign

0.076

T;T;T

MutationAssessor

Uncertain

2.9

M;.;.

PrimateAI

Pathogenic

0.86

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.64

MVP

0.17

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.15

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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