12-121712932-C-G

Variant names:

• chr12-121712932-C-G
• rs778133052
• NM_001080825.2:c.37C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001080825.2(TMEM120B):​c.37C>G​(p.His13Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM120B NM_001080825.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.43
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061388135).

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.37C>G	p.His13Asp	missense	Exon 1 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.37C>G	p.His13Asp	missense	Exon 1 of 12	ENSP00000404991.2	A0PK00
	TMEM120B	ENST00000342607.10	TSL:2	n.37C>G		non_coding_transcript_exon	Exon 1 of 13	ENSP00000345152.6	A0PK00

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	21
DANN	Benign	0.67
DEOGEN2	Benign	0.0067	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.6	N
PhyloP100		1.4
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	0.55	N
REVEL	Benign	0.098
Sift	Benign	0.57	T
Sift4G	Benign	0.67	T
Polyphen		0.0	B
Vest4		0.34
MutPred		0.41		Loss of MoRF binding (P = 0.4183)
MVP		0.067
MPC		0.64
ClinPred		0.072	T
GERP RS		2.1
PromoterAI		0.082	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.13
gMVP		0.18
Mutation Taster		=90/10	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: rs778133052; hg19: chr12-122150838;