chr12-121748329-C-G

Variant names:

• chr12-121748329-C-G
• NM_001080825.2:c.192C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001080825.2(TMEM120B):​c.192C>G​(p.Cys64Trp) 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 1,457,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TMEM120B NM_001080825.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.436

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

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=0.23113942).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM120B	NM_001080825.2	c.192C>G	p.Cys64Trp	missense_variant	Exon 3 of 12	ENST00000449592.7	NP_001074294.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM120B	ENST00000449592.7	c.192C>G	p.Cys64Trp	missense_variant	Exon 3 of 12	1	NM_001080825.2	ENSP00000404991.2
TMEM120B	ENST00000541467.1	c.129C>G	p.Cys43Trp	missense_variant	Exon 2 of 10	5		ENSP00000442105.1
TMEM120B	ENST00000342607.10	n.192C>G		non_coding_transcript_exon_variant	Exon 3 of 13	2		ENSP00000345152.6

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457544 Hom.: 0 Cov.: 29 AF XY: 0.00000276 AC XY: 2 AN XY: 724978

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 17, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.192C>G (p.C64W) alteration is located in exon 3 (coding exon 3) of the TMEM120B gene. This alteration results from a C to G substitution at nucleotide position 192, causing the cysteine (C) at amino acid position 64 to be replaced by a tryptophan (W). 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	Benign	0.16
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T;.
Eigen	Benign	-0.042
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.8	M;.
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.7	D;D
REVEL	Benign	0.14
Sift	Benign	0.12	T;T
Sift4G	Benign	0.11	T;T
Polyphen		0.57	P;.
Vest4		0.34
MutPred		0.33		Gain of MoRF binding (P = 0.0212);.;
MVP		0.11
MPC		1.2
ClinPred		0.98	D
GERP RS		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.48
gMVP		0.46

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-122186235;