chr9-25677912-C-G

Variant names:

• chr9-25677912-C-G
• rs1340738445
• NM_001004125.3:c.401G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001004125.3(TUSC1):​c.401G>C​(p.Ser134Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,424,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S134N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: TUSC1 NM_001004125.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.462
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06505695).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004125.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUSC1	NM_001004125.3	MANE Select	c.401G>C	p.Ser134Thr	missense	Exon 1 of 1	NP_001004125.2	Q2TAM9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUSC1	ENST00000358022.6	TSL:6 MANE Select	c.401G>C	p.Ser134Thr	missense	Exon 1 of 1	ENSP00000350716.4	Q2TAM9

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1424122 Hom.: 0 Cov.: 73 AF XY: 0.00 AC XY: 0 AN XY: 706104

African (AFR) AF: 0.00 AC: 0 AN: 32824

American (AMR) AF: 0.0000244 AC: 1 AN: 40958

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25520

East Asian (EAS) AF: 0.00 AC: 0 AN: 38010

South Asian (SAS) AF: 0.00 AC: 0 AN: 82296

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42672

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5710

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1097064

Other (OTH) AF: 0.00 AC: 0 AN: 59068

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	8.6
DANN	Benign	0.85
DEOGEN2	Benign	0.0034	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.28	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.46
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.035
Sift	Benign	0.20	T
Sift4G	Benign	0.55	T
Polyphen		0.065	B
Vest4		0.072
MutPred		0.054		Loss of MoRF binding (P = 0.1151)
MVP		0.030
MPC		0.58
ClinPred		0.084	T
GERP RS		0.45
Varity_R		0.041
gMVP		0.014
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs1340738445; hg19: chr9-25677910;