11-2316289-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_139022.3(TSPAN32):c.604A>G(p.Thr202Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TSPAN32 NM_139022.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0170

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1193904).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSPAN32	NM_139022.3	c.604A>G	p.Thr202Ala	missense_variant	7/10	ENST00000182290.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSPAN32	ENST00000182290.9	c.604A>G	p.Thr202Ala	missense_variant	7/10	1	NM_139022.3	P2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1450682 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 721086

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.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 02, 2023

The c.604A>G (p.T202A) alteration is located in exon 7 (coding exon 7) of the TSPAN32 gene. This alteration results from a A to G substitution at nucleotide position 604, causing the threonine (T) at amino acid position 202 to be replaced by an alanine (A). 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	0.10
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
Cadd	Benign	12
Dann	Benign	0.67
DEOGEN2	Benign	0.15	T;T;.;.;T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.61	T;T;T;T;.
M_CAP	Benign	0.068	D
MetaRNN	Benign	0.12	T;T;T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.3	L;.;L;.;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.3	N;.;N;N;N
REVEL	Benign	0.17
Sift	Benign	0.12	T;.;T;T;T
Sift4G	Benign	0.37	T;T;T;T;T
Polyphen		0.026	B;B;B;.;B
Vest4		0.10
MutPred		0.51		Loss of disorder (P = 0.2156);.;Loss of disorder (P = 0.2156);.;.;
MVP		0.57
MPC		0.052
ClinPred		0.054	T
GERP RS		-0.056
Varity_R		0.045
gMVP		0.37

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-2337519;