rs1554812687

Variant names:

• chr9-132896437-T-A
• NM_000368.5:c.3293A>T

Your query was ambiguous. Multiple possible variants found:

• chr9-132896437-T-A
• chr9-132896437-T-C
• chr9-132896437-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000368.5(TSC1):​c.3293A>T​(p.Asn1098Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TSC1 NM_000368.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.41

Genes affected

TSC1 (HGNC:12362): (TSC complex subunit 1) This gene is a tumor suppressor gene that encodes the growth inhibitory protein hamartin. The encoded protein interacts with and stabilizes the GTPase activating protein tuberin. This hamartin-tuberin complex negatively regulates mammalian target of rapamycin complex 1 (mTORC1) signaling which is a major regulator of anabolic cell growth. This protein also functions as a co-chaperone for Hsp90 that inhibits its ATPase activity. This protein functions as a facilitator of Hsp90-mediated folding of kinase and non-kinase clients, including TSC2 and thereby preventing their ubiquitination and proteasomal degradation. Mutations in this gene have been associated with tuberous sclerosis and lymphangioleiomyomatosis. [provided by RefSeq, May 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSC1	NM_000368.5	c.3293A>T	p.Asn1098Ile	missense_variant	Exon 23 of 23	ENST00000298552.9	NP_000359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSC1	ENST00000298552.9	c.3293A>T	p.Asn1098Ile	missense_variant	Exon 23 of 23	1	NM_000368.5	ENSP00000298552.3
TSC1	ENST00000490179.4	c.3293A>T	p.Asn1098Ile	missense_variant	Exon 24 of 24	3		ENSP00000495533.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.59	D;.;D;.;.;D;.;D;.;.;.
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.95	.;D;D;D;D;.;.;.;D;D;.
M_CAP	Pathogenic	0.31	D
MetaRNN	Uncertain	0.56	D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.60	D
MutationAssessor	Uncertain	2.4	M;.;M;.;.;M;.;M;.;.;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-2.6	D;D;D;.;.;.;.;.;.;.;.
REVEL	Uncertain	0.57
Sift	Pathogenic	0.0	D;D;D;.;.;.;.;.;.;.;.
Sift4G	Pathogenic	0.0010	D;D;D;.;.;.;.;.;.;.;.
Polyphen		1.0	D;.;D;.;.;D;.;D;.;.;.
Vest4		0.49
MutPred		0.30		Loss of loop (P = 0.0986);.;Loss of loop (P = 0.0986);.;.;Loss of loop (P = 0.0986);.;Loss of loop (P = 0.0986);.;.;.;
MVP		0.75
MPC		0.65
ClinPred		0.96	D
GERP RS		5.6
Varity_R		0.65
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-135771824;