12-3278996-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_006675.5(TSPAN9):ā€‹c.260T>Gā€‹(p.Phe87Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,614,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000075 ( 0 hom. )

Consequence

TSPAN9
NM_006675.5 missense

Scores

14
4
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.97
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.91

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TSPAN9NM_006675.5 linkc.260T>G p.Phe87Cys missense_variant 5/9 ENST00000011898.10 NP_006666.1 O75954

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TSPAN9ENST00000011898.10 linkc.260T>G p.Phe87Cys missense_variant 5/91 NM_006675.5 ENSP00000011898.5 O75954

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152210
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251440
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135898
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000145
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
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:
0.00000752
AC:
11
AN:
1461844
Hom.:
0
Cov.:
31
AF XY:
0.00000550
AC XY:
4
AN XY:
727224
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000134
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:
0.00000270
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152210
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.0000165
AC:
2

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 submitterclinical testingAmbry GeneticsJan 23, 2024The c.260T>G (p.F87C) alteration is located in exon 5 (coding exon 3) of the TSPAN9 gene. This alteration results from a T to G substitution at nucleotide position 260, causing the phenylalanine (F) at amino acid position 87 to be replaced by a cysteine (C). 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
Pathogenic
0.64
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Pathogenic
0.38
CADD
Pathogenic
29
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.45
T;T;.;T
Eigen
Pathogenic
0.84
Eigen_PC
Pathogenic
0.77
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.92
D;.;D;D
M_CAP
Pathogenic
0.30
D
MetaRNN
Pathogenic
0.91
D;D;D;D
MetaSVM
Uncertain
0.59
D
MutationAssessor
Pathogenic
3.1
M;M;.;.
PrimateAI
Pathogenic
0.79
T
PROVEAN
Pathogenic
-7.3
D;D;.;D
REVEL
Pathogenic
0.88
Sift
Pathogenic
0.0
D;D;.;D
Sift4G
Pathogenic
0.0
D;D;.;D
Polyphen
1.0
D;D;.;.
Vest4
0.92
MutPred
0.70
Gain of catalytic residue at V89 (P = 8e-04);Gain of catalytic residue at V89 (P = 8e-04);.;Gain of catalytic residue at V89 (P = 8e-04);
MVP
0.92
MPC
1.7
ClinPred
0.99
D
GERP RS
5.4
Varity_R
0.87
gMVP
0.87

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.

Other links and lift over

dbSNP: rs754646751; hg19: chr12-3388162; API