Variant 12-3281799-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006675.5(TSPAN9):c.630G>A(p.Met210Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,846 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: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

TSPAN9
NM_006675.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.46

Variant links:

Genes affected

TSPAN9 (HGNC:21640): (tetraspanin 9) The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. Alternatively spliced transcripts encoding the same protein have been identified. [provided by RefSeq, Nov 2009]

TSPAN9 links:

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ACMG classification

Classification made for transcript

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=0.21738589).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPAN9	NM_006675.5 linkuse as main transcript	c.630G>A	p.Met210Ile	missense_variant	8/9	ENST00000011898.10	NP_006666.1	O75954

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TSPAN9	ENST00000011898.10 linkuse as main transcript	c.630G>A	p.Met210Ile	missense_variant	8/9	1	NM_006675.5	ENSP00000011898.5	O75954
TSPAN9	ENST00000407263.2 linkuse as main transcript	c.630G>A	p.Met210Ile	missense_variant	6/6	5		ENSP00000384488.1	B5MD23
TSPAN9	ENST00000537971.5 linkuse as main transcript	c.630G>A	p.Met210Ile	missense_variant	7/8	3		ENSP00000444799.1	O75954
TSPAN9	ENST00000649909.1 linkuse as main transcript	c.*43G>A		downstream_gene_variant				ENSP00000497370.1	A0A3B3IST1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251178

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135778

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461846

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

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.:

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

Oct 17, 2023

The c.630G>A (p.M210I) alteration is located in exon 8 (coding exon 6) of the TSPAN9 gene. This alteration results from a G to A substitution at nucleotide position 630, causing the methionine (M) at amino acid position 210 to be replaced by an isoleucine (I). 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

0.44

BayesDel_addAF

Uncertain

0.073

BayesDel_noAF

Uncertain

0.090

CADD

Uncertain

DANN

Benign

0.87

DEOGEN2

Benign

0.057

T;T;T

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.096

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.87

D;.;D

M_CAP

Benign

0.031

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

-0.76

N;N;.

PrimateAI

Uncertain

0.69

PROVEAN

Benign

0.62

N;N;N

REVEL

Uncertain

0.45

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.044

B;B;.

Vest4

0.43

MutPred

0.47

Gain of catalytic residue at L213 (P = 0);Gain of catalytic residue at L213 (P = 0);Gain of catalytic residue at L213 (P = 0);

MVP

0.91

MPC

0.57

ClinPred

0.27

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.24

gMVP

0.92

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

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