Variant chr11-2316235-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_139022.3(TSPAN32):c.550C>T(p.Leu184Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TSPAN32
NM_139022.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.598

Variant links:

Genes affected

TSPAN32 (HGNC:13410): (tetraspanin 32) This gene, which is a member of the tetraspanin superfamily, is one of several tumor-suppressing subtransferable fragments located in the imprinted gene domain of chromosome 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian and breast cancers. This gene is located among several imprinted genes; however, this gene, as well as the tumor-suppressing subchromosomal transferable fragment 4, escapes imprinting. This gene may play a role in malignancies and diseases that involve this region, and it is also involved in hematopoietic cell function. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

TSPAN32 links:

TSPAN32 (HGNC:):

TSPAN32 links:

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ACMG classification

Classification made for transcript

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/exons	MANE	Protein	UniProt
TSPAN32	NM_139022.3 linkuse as main transcript	c.550C>T	p.Leu184Phe	missense_variant	7/10	ENST00000182290.9	NP_620591.3	Q96QS1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPAN32	ENST00000182290.9 linkuse as main transcript	c.550C>T	p.Leu184Phe	missense_variant	7/10	1	NM_139022.3	ENSP00000182290.5		Q96QS1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1433796

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

711142

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000825

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2024

The c.550C>T (p.L184F) alteration is located in exon 7 (coding exon 7) of the TSPAN32 gene. This alteration results from a C to T substitution at nucleotide position 550, causing the leucine (L) at amino acid position 184 to be replaced by a phenylalanine (F). 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

Uncertain

0.45

BayesDel_addAF

Uncertain

0.016

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.79

D;T;.;.;T

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.10

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.79

T;T;T;T;.

M_CAP

Pathogenic

0.29

MetaRNN

Uncertain

0.52

D;D;D;D;D

MetaSVM

Uncertain

-0.18

MutationAssessor

Benign

1.8

L;.;L;.;.

PrimateAI

Benign

0.38

PROVEAN

Benign

-2.1

N;.;N;N;N

REVEL

Uncertain

0.56

Sift

Uncertain

0.0090

D;.;D;D;D

Sift4G

Uncertain

0.0090

D;D;D;D;D

Polyphen

1.0

D;D;D;.;D

Vest4

0.42

MutPred

0.61

Loss of catalytic residue at L184 (P = 0.0081);.;Loss of catalytic residue at L184 (P = 0.0081);.;.;

MVP

0.77

MPC

0.28

ClinPred

0.82

GERP RS

2.9

Varity_R

0.15

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.30

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.30

Position offset: 6

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over