12-121761722-A-G

Variant names:

• chr12-121761722-A-G
• rs1463654356
• NM_001080825.2:c.535A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001080825.2(TMEM120B):​c.535A>G​(p.Ile179Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I179L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TMEM120B NM_001080825.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.32
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2470873).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080825.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM120B	NM_001080825.2	MANE Select	c.535A>G	p.Ile179Val	missense	Exon 6 of 12	NP_001074294.2	A0PK00

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM120B	ENST00000449592.7	TSL:1 MANE Select	c.535A>G	p.Ile179Val	missense	Exon 6 of 12	ENSP00000404991.2	A0PK00
	TMEM120B	ENST00000541467.1	TSL:5	c.472A>G	p.Ile158Val	missense	Exon 5 of 10	ENSP00000442105.1	H0YG77
	TMEM120B	ENST00000540377.1	TSL:3	c.-228A>G		5_prime_UTR	Exon 2 of 6	ENSP00000446159.1	F5H465

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Benign	0.94
DEOGEN2	Benign	0.015	T
Eigen	Benign	0.067
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		9.3
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.19
Sift	Benign	0.28	T
Sift4G	Benign	1.0	T
Polyphen		0.17	B
Vest4		0.36
MutPred		0.40		Gain of catalytic residue at L178 (P = 0)
MVP		0.16
MPC		0.51
ClinPred		0.66	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.078
gMVP		0.29
Mutation Taster		=171/129	polymorphism

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

Other links and lift over

dbSNP: rs1463654356; hg19: chr12-122199628;