Variant 9-25677730-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001004125.3(TUSC1):c.583T>G(p.Ser195Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000147 in 1,568,714 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000085 ( 0 hom. )

Consequence

TUSC1
NM_001004125.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.388

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02712518).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUSC1	NM_001004125.3 linkuse as main transcript	c.583T>G	p.Ser195Ala	missense_variant	1/1	ENST00000358022.6	NP_001004125.2	Q2TAM9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUSC1	ENST00000358022.6 linkuse as main transcript	c.583T>G	p.Ser195Ala	missense_variant	1/1	6	NM_001004125.3	ENSP00000350716.4		Q2TAM9

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000226

AC:

AN:

177146

Hom.:

AF XY:

0.0000209

AC XY:

AN XY:

95904

show subpopulations

Gnomad AFR exome

AF:

0.000101

Gnomad AMR exome

AF:

0.000107

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:

0.00000847

AC:

AN:

1416534

Hom.:

Cov.:

AF XY:

0.00000999

AC XY:

AN XY:

700450

show subpopulations

Gnomad4 AFR exome

AF:

0.000185

Gnomad4 AMR exome

AF:

0.000153

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

AF:

0.0000723

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.000265

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000113

ExAC

AF:

0.00000850

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 04, 2022

The c.592T>G (p.S198A) alteration is located in exon 1 (coding exon 1) of the TUSC1 gene. This alteration results from a T to G substitution at nucleotide position 592, causing the serine (S) at amino acid position 198 to be replaced by an alanine (A). 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

0.067

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.2

DANN

Benign

0.83

DEOGEN2

Benign

0.0062

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.20

M_CAP

Benign

0.039

MetaRNN

Benign

0.027

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.46

REVEL

Benign

0.035

Sift

Uncertain

0.024

Sift4G

Benign

0.42

Polyphen

0.0030

Vest4

0.032

MutPred

0.076

Loss of phosphorylation at S198 (P = 0.0013);

MVP

0.014

MPC

0.50

ClinPred

0.051

GERP RS

-4.5

Varity_R

0.053

gMVP

0.0039

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