GeneBe

rs1207228302

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012338.4(TSPAN12):​c.877G>T​(p.Ala293Ser) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A293V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

TSPAN12
NM_012338.4 missense

Scores

1
5
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.14

Publications

0 publications found
Variant links:
Genes affected
TSPAN12 (HGNC:21641): (tetraspanin 12) 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. [provided by RefSeq, Jul 2008]
TSPAN12 Gene-Disease associations (from GenCC):
  • exudative vitreoretinopathy 5
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
  • TSPAN12-related exudative vitreoretinopathy
    Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
  • exudative vitreoretinopathy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16779897).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012338.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
TSPAN12
NM_012338.4
MANE Select
c.877G>Tp.Ala293Ser
missense
Exon 8 of 8NP_036470.1O95859-1

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
TSPAN12
ENST00000222747.8
TSL:1 MANE Select
c.877G>Tp.Ala293Ser
missense
Exon 8 of 8ENSP00000222747.3O95859-1
TSPAN12
ENST00000415871.5
TSL:5
c.877G>Tp.Ala293Ser
missense
Exon 9 of 9ENSP00000397699.1O95859-1
TSPAN12
ENST00000854320.1
c.877G>Tp.Ala293Ser
missense
Exon 9 of 9ENSP00000524379.1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
57
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.084
BayesDel_addAF
Benign
-0.055
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.096
T
Eigen
Benign
0.076
Eigen_PC
Uncertain
0.26
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.78
T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.17
T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
0.81
L
PhyloP100
2.1
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-0.21
N
REVEL
Benign
0.043
Sift
Uncertain
0.013
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.39
B
Vest4
0.14
MutPred
0.26
Gain of loop (P = 0.0166)
MVP
0.28
MPC
0.10
ClinPred
0.54
D
GERP RS
5.8
Varity_R
0.10
gMVP
0.57
Mutation Taster
=80/20
polymorphism

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

Other links and lift over

dbSNP: rs1207228302; hg19: chr7-120428687; API