9-25677912-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001004125.3(TUSC1):​c.401G>A​(p.Ser134Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000146 in 1,576,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

TUSC1
NM_001004125.3 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.462
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.07141504).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TUSC1NM_001004125.3 linkc.401G>A p.Ser134Asn 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
TUSC1ENST00000358022.6 linkc.401G>A p.Ser134Asn missense_variant Exon 1 of 1 6 NM_001004125.3 ENSP00000350716.4 Q2TAM9

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152224
Hom.:
0
Cov.:
34
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:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000119
AC:
17
AN:
1424124
Hom.:
0
Cov.:
73
AF XY:
0.00000991
AC XY:
7
AN XY:
706104
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:
0.0000146
Gnomad4 OTH exome
AF:
0.0000169
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152224
Hom.:
0
Cov.:
34
AF XY:
0.0000403
AC XY:
3
AN XY:
74364
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:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000264

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 25, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.410G>A (p.S137N) 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 410, causing the serine (S) at amino acid position 137 to be replaced by an asparagine (N). 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
0.13
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.76
CADD
Benign
9.8
DANN
Benign
0.93
DEOGEN2
Benign
0.0033
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.067
N
LIST_S2
Benign
0.33
T
M_CAP
Uncertain
0.14
D
MetaRNN
Benign
0.071
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
N
PrimateAI
Pathogenic
0.82
D
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.048
Sift
Benign
0.16
T
Sift4G
Benign
0.48
T
Polyphen
0.034
B
Vest4
0.041
MVP
0.030
MPC
0.58
ClinPred
0.26
T
GERP RS
0.45
Varity_R
0.058
gMVP
0.0085

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.

Other links and lift over

dbSNP: rs1340738445; hg19: chr9-25677910; API