Variant 7-75987756-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000493111.7(TMEM120A):c.746G>A(p.Arg249Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000295 in 1,612,198 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00097 ( 10 hom., cov: 31)

Exomes 𝑓: 0.00023 ( 1 hom. )

Consequence

TMEM120A
ENST00000493111.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.06

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01767397).

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM120A	NM_031925.3 linkuse as main transcript	c.746G>A	p.Arg249Gln	missense_variant	9/12	ENST00000493111.7	NP_114131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM120A	ENST00000493111.7 linkuse as main transcript	c.746G>A	p.Arg249Gln	missense_variant	9/12	1	NM_031925.3	ENSP00000473983	P1	Q9BXJ8-1

Frequencies

GnomAD3 genomes

AF:

0.000966

AC:

147

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.127

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000106

AC:

AN:

245624

Hom.:

AF XY:

0.000119

AC XY:

AN XY:

134274

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000467

Gnomad NFE exome

AF:

0.000217

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000225

AC:

329

AN:

1459964

Hom.:

Cov.:

AF XY:

0.000216

AC XY:

157

AN XY:

726252

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000281

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000966

AC:

147

AN:

152234

Hom.:

Cov.:

AF XY:

0.000861

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000297

Hom.:

Bravo

AF:

0.00132

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000361

AC:

ExAC

AF:

0.0000834

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

Oct 22, 2021

The c.746G>A (p.R249Q) alteration is located in exon 9 (coding exon 9) of the TMEM120A gene. This alteration results from a G to A substitution at nucleotide position 746, causing the arginine (R) at amino acid position 249 to be replaced by a glutamine (Q). 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

Pathogenic

0.88

BayesDel_addAF

Benign

-0.00054

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

DANN

Benign

0.82

DEOGEN2

Benign

0.16

T;.;.

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.95

D;D;D

MetaRNN

Benign

0.018

T;T;T

MutationAssessor

Uncertain

2.7

M;.;.

PrimateAI

Uncertain

0.70

Sift4G

Uncertain

0.011

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.78

MVP

0.14

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.086

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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