chr9-25677766-C-G

Variant names:

• chr9-25677766-C-G
• rs756909069
• NM_001004125.3:c.547G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001004125.3(TUSC1):​c.547G>C​(p.Gly183Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000506 in 1,580,988 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 (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: TUSC1 NM_001004125.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.180
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07700944).

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.547G>C	p.Gly183Arg	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.547G>C	p.Gly183Arg	missense	Exon 1 of 1	ENSP00000350716.4	Q2TAM9

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152216 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

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

GnomAD4 exome AF: 0.00000280 AC: 4 AN: 1428772 Hom.: 0 Cov.: 73 AF XY: 0.00000282 AC XY: 2 AN XY: 707990

African (AFR) AF: 0.00 AC: 0 AN: 32740

American (AMR) AF: 0.0000246 AC: 1 AN: 40646

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25516

East Asian (EAS) AF: 0.00 AC: 0 AN: 37702

South Asian (SAS) AF: 0.00 AC: 0 AN: 82092

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49078

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5680

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1096330

Other (OTH) AF: 0.0000509 AC: 3 AN: 58988

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152216 Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2 AN XY: 74362

African (AFR) AF: 0.00 AC: 0 AN: 41464

American (AMR) AF: 0.000262 AC: 4 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000869

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	0.11
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	14
DANN	Benign	0.96
DEOGEN2	Benign	0.0041	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.092	N
LIST_S2	Benign	0.52	T
M_CAP	Uncertain	0.28	D
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.18
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	0.12	N
REVEL	Benign	0.039
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.020	D
Polyphen		0.013	B
Vest4		0.056
MutPred		0.13		Gain of solvent accessibility (P = 0.0037)
MVP		0.11
MPC		0.71
ClinPred		0.092	T
GERP RS		1.8
Varity_R		0.042
gMVP		0.0064
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: rs756909069; hg19: chr9-25677764;