Genetic Variant TUSC1:p.Gly53Ser (chr9-25678156-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001004125.3(TUSC1):c.157G>A(p.Gly53Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000409 in 1,467,252 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000043 ( 0 hom. )

Consequence

TUSC1
NM_001004125.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.76

Variant links:

Genes affected

TUSC1 (HGNC:31010): (tumor suppressor candidate 1) This gene is located within the region of chromosome 9p that harbors tumor suppressor genes critical in carcinogenesis. It is an intronless gene which is downregulated in non-small-cell lung cancer and small-cell lung cancer cell lines, suggesting that it may play a role in lung tumorigenesis. [provided by RefSeq, Jul 2008]

TUSC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
TUSC1	NM_001004125.3 link	c.157G>A	p.Gly53Ser	missense_variant	Exon 1 of 1	ENST00000358022.6	NP_001004125.2	Q2TAM9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUSC1	ENST00000358022.6 link	c.157G>A	p.Gly53Ser	missense_variant	Exon 1 of 1	6	NM_001004125.3	ENSP00000350716.4		Q2TAM9

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151398

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000443

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000322

AC:

AN:

62128

Hom.:

AF XY:

0.0000278

AC XY:

AN XY:

35976

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000426

Gnomad OTH exome

AF:

0.000569

GnomAD4 exome

AF:

0.0000433

AC:

AN:

1315854

Hom.:

Cov.:

AF XY:

0.0000448

AC XY:

AN XY:

647350

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000524

Gnomad4 OTH exome

AF:

0.0000366

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151398

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73924

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000443

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.166G>A (p.G56S) alteration is located in exon 1 (coding exon 1) of the TUSC1 gene. This alteration results from a G to A substitution at nucleotide position 166, causing the glycine (G) at amino acid position 56 to be replaced by a serine (S). 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

Pathogenic

0.61

BayesDel_addAF

Uncertain

0.048

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0098

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.56

M_CAP

Pathogenic

0.99

MetaRNN

Uncertain

0.71

MetaSVM

Uncertain

0.070

MutationAssessor

Benign

0.63

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.43

REVEL

Uncertain

0.40

Sift

Uncertain

0.019

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.49

MutPred

0.22

Gain of phosphorylation at G56 (P = 0.0277);

MVP

0.87

MPC

1.6

ClinPred

0.27

GERP RS

2.9

Varity_R

0.094

gMVP

0.042

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over