chr4-98486772-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_005723.4(TSPAN5):​c.245G>A​(p.Gly82Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 (★).

Frequency

Genomes: not found (cov: 31)

Consequence

TSPAN5
NM_005723.4 missense

Scores

16
2
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.75
Variant links:
Genes affected
TSPAN5 (HGNC:17753): (tetraspanin 5) 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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.974

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TSPAN5NM_005723.4 linkc.245G>A p.Gly82Glu missense_variant Exon 3 of 8 ENST00000305798.8 NP_005714.2 P62079

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TSPAN5ENST00000305798.8 linkc.245G>A p.Gly82Glu missense_variant Exon 3 of 8 1 NM_005723.4 ENSP00000307701.3 P62079

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
31

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 31, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.245G>A (p.G82E) alteration is located in exon 3 (coding exon 3) of the TSPAN5 gene. This alteration results from a G to A substitution at nucleotide position 245, causing the glycine (G) at amino acid position 82 to be replaced by a glutamic acid (E). 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
1.0
BayesDel_addAF
Pathogenic
0.47
D
BayesDel_noAF
Pathogenic
0.43
CADD
Pathogenic
30
DANN
Uncertain
0.97
DEOGEN2
Pathogenic
0.80
D;.;.;.
Eigen
Pathogenic
1.1
Eigen_PC
Pathogenic
0.97
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.99
D;D;D;D
M_CAP
Pathogenic
0.34
D
MetaRNN
Pathogenic
0.97
D;D;D;D
MetaSVM
Pathogenic
0.96
D
MutationAssessor
Pathogenic
4.1
H;.;.;.
PrimateAI
Pathogenic
0.92
D
PROVEAN
Pathogenic
-7.2
D;D;D;D
REVEL
Pathogenic
0.94
Sift
Pathogenic
0.0
D;D;D;D
Sift4G
Uncertain
0.0030
D;D;.;D
Polyphen
1.0
D;.;.;.
Vest4
0.99
MutPred
0.88
Loss of catalytic residue at A83 (P = 0.1965);.;.;.;
MVP
0.89
MPC
2.4
ClinPred
1.0
D
GERP RS
5.5
Varity_R
0.95
gMVP
1.0

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: chr4-99407923; API