chr9-25677708-G-A

Variant names:

• chr9-25677708-G-A
• rs1440619033
• NM_001004125.3:c.605C>T

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.605C>T​(p.Ser202Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00002 in 1,403,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: TUSC1 NM_001004125.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.473
• 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=0.04377857).

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.605C>T	p.Ser202Leu	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.605C>T	p.Ser202Leu	missense	Exon 1 of 1	ENSP00000350716.4	Q2TAM9

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.0000186 AC: 3 AN: 160960 AF XY: 0.0000115

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000818

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000321

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000200 AC: 28 AN: 1403176 Hom.: 0 Cov.: 74 AF XY: 0.00000866 AC XY: 6 AN XY: 692502

African (AFR) AF: 0.00 AC: 0 AN: 31992

American (AMR) AF: 0.00 AC: 0 AN: 37506

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25102

East Asian (EAS) AF: 0.00 AC: 0 AN: 36426

South Asian (SAS) AF: 0.0000125 AC: 1 AN: 79886

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47446

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4680

European-Non Finnish (NFE) AF: 0.0000250 AC: 27 AN: 1082152

Other (OTH) AF: 0.00 AC: 0 AN: 57986

GnomAD4 genome Cov.: 34

Alfa AF: 0.0000283 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	11
DANN	Benign	0.94
DEOGEN2	Benign	0.0027	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.47
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.071
Sift	Benign	0.28	T
Sift4G	Uncertain	0.023	D
Polyphen		0.0	B
Vest4		0.070
MutPred		0.12		Loss of phosphorylation at S205 (P = 0.0015)
MVP		0.040
MPC		0.59
ClinPred		0.034	T
GERP RS		1.1
Varity_R		0.034
gMVP		0.0052
Mutation Taster		=100/0	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: rs1440619033; hg19: chr9-25677706; COSMIC: COSV63662015;