Variant 12-121743648-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001080825.2(TMEM120B):c.89A>G(p.Lys30Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TMEM120B
NM_001080825.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.960

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04989621).

BP6

Variant 12-121743648-A-G is Benign according to our data. Variant chr12-121743648-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3178476.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM120B	NM_001080825.2 linkuse as main transcript	c.89A>G	p.Lys30Arg	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.89A>G	p.Lys30Arg	missense_variant	2/12	1	NM_001080825.2	ENSP00000404991.2	A0PK00
TMEM120B	ENST00000541467.1 linkuse as main transcript	c.26A>G	p.Lys9Arg	missense_variant	1/10	5		ENSP00000442105.1	H0YG77
TMEM120B	ENST00000342607.10 linkuse as main transcript	n.89A>G		non_coding_transcript_exon_variant	2/13	2		ENSP00000345152.6	A0PK00

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461546

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727054

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000313

Hom.:

Bravo

AF:

0.0000453

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 08, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

1.1

DANN

Benign

0.74

DEOGEN2

Benign

0.0074

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.65

T;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.050

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

N;.

PrimateAI

Benign

0.37

PROVEAN

Benign

0.17

N;N

REVEL

Benign

0.069

Sift

Benign

0.82

T;T

Sift4G

Benign

0.57

T;T

Polyphen

0.0

B;.

Vest4

0.13

MutPred

0.47

Gain of catalytic residue at I28 (P = 0.0037);.;

MVP

0.12

MPC

0.38

ClinPred

0.068

GERP RS

-7.3

Varity_R

0.056

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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