Variant chr11-2302174-G-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.25G>T(p.Val9Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000158 in 1,268,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

TSPAN32
NM_139022.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.538

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:

C11orf21 (HGNC:13231): (chromosome 11 open reading frame 21) Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

C11orf21 links:

Genome browser will be placed here

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.25G>T	p.Val9Phe	missense_variant	1/10	ENST00000182290.9	NP_620591.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPAN32	ENST00000182290.9 linkuse as main transcript	c.25G>T	p.Val9Phe	missense_variant	1/10	1	NM_139022.3	ENSP00000182290	P2	Q96QS1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

125306

Hom.:

AF XY:

0.0000300

AC XY:

AN XY:

66742

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000968

Gnomad SAS exome

AF:

0.000115

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000158

AC:

AN:

1268074

Hom.:

Cov.:

AF XY:

0.00000325

AC XY:

AN XY:

614490

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000291

Gnomad4 SAS exome

AF:

0.0000195

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000881

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

Mar 29, 2023

The c.25G>T (p.V9F) alteration is located in exon 1 (coding exon 1) of the TSPAN32 gene. This alteration results from a G to T substitution at nucleotide position 25, causing the valine (V) at amino acid position 9 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

Benign

0.16

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.089

T;.

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.51

T;T

M_CAP

Benign

0.028

MetaRNN

Benign

0.066

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.55

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.98

N;N

REVEL

Benign

0.062

Sift

Benign

0.033

D;D

Sift4G

Uncertain

0.037

D;D

Polyphen

0.026

B;.

Vest4

0.37

MutPred

0.51

Gain of MoRF binding (P = 0.1202);Gain of MoRF binding (P = 0.1202);

MVP

0.16

MPC

0.27

ClinPred

0.50

GERP RS

-3.4

Varity_R

0.092

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.42

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.42

Position offset: -2

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