12-121770960-T-C

Position:

• chr12-121770960-T-C

Variant summary

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

The NM_001080825.2(TMEM120B):​c.605T>C​(p.Val202Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 6.24

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM120B	NM_001080825.2	c.605T>C	p.Val202Ala	missense_variant	7/12	ENST00000449592.7	NP_001074294.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM120B	ENST00000449592.7	c.605T>C	p.Val202Ala	missense_variant	7/12	1	NM_001080825.2	ENSP00000404991.2
TMEM120B	ENST00000541467.1	c.542T>C	p.Val181Ala	missense_variant	6/10	5		ENSP00000442105.1
TMEM120B	ENST00000540377.1	c.-211-2461T>C		intron_variant		3		ENSP00000446159.1
TMEM120B	ENST00000342607.10	n.605T>C		non_coding_transcript_exon_variant	7/13	2		ENSP00000345152.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Exstrophy-epispadias complex Uncertain:1

Uncertain significance, criteria provided, single submitter

curation

Obstetrics and Gynecology Department, Johns Hopkins School Of Medicine

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;.
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	D;T
M_CAP	Uncertain	0.096	D
MetaRNN	Uncertain	0.70	D;D
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	1.9	L;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.5	D;D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.037	D;D
Polyphen		0.011	B;.
Vest4		0.91
MutPred		0.73		Gain of catalytic residue at L204 (P = 0);.;
MVP		0.36
MPC		0.64
ClinPred		0.95	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.55
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

Other links and lift over

dbSNP: rs1277714338; hg19: chr12-122208866;