3-50326153-C-G

Variant names:

• chr3-50326153-C-G
• rs140522021
• NM_007275.3:c.301G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_007275.3(TUSC2):​c.301G>C​(p.Val101Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000692 in 1,445,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TUSC2 NM_007275.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.72

Genes affected

TUSC2 (HGNC:17034): (tumor suppressor 2, mitochondrial calcium regulator) Predicted to be involved in inflammatory response and regulation of mitochondrial membrane potential. Predicted to act upstream of or within several processes, including natural killer cell differentiation; neutrophil-mediated killing of gram-negative bacterium; and regulation of cytokine production. Predicted to be active in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40553004).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUSC2	NM_007275.3	c.301G>C	p.Val101Leu	missense_variant	Exon 3 of 3	ENST00000232496.5	NP_009206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUSC2	ENST00000232496.5	c.301G>C	p.Val101Leu	missense_variant	Exon 3 of 3	1	NM_007275.3	ENSP00000232496.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000446 AC: 1 AN: 223976 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 120350

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000322

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1445596 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 717426

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000240

Gnomad4 ASJ exome AF: 0.00

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: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.41	T
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.27
Sift	Uncertain	0.029	D
Sift4G	Benign	0.062	T
Polyphen		1.0	D
Vest4		0.31
MutPred		0.32		Gain of catalytic residue at V101 (P = 0.0429);
MVP		0.43
MPC		0.70
ClinPred		0.81	D
GERP RS		5.4
Varity_R		0.21
gMVP		0.54

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

LitVar

Other links and lift over

dbSNP: rs140522021; hg19: chr3-50363584;