GeneBe

rs2069111091

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004615.4(TSPAN7):​c.43C>G​(p.Leu15Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. L15F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 21)

Consequence

TSPAN7
NM_004615.4 missense

Scores

3
4
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.32

Publications

0 publications found
Variant links:
Genes affected
TSPAN7 (HGNC:11854): (tetraspanin 7) 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. This encoded protein is a cell surface glycoprotein and may have a role in the control of neurite outgrowth. It is known to complex with integrins. This gene is associated with X-linked cognitive disability and neuropsychiatric diseases such as Huntington's chorea, fragile X syndrome and myotonic dystrophy. [provided by RefSeq, Jul 2008]
TSPAN7 Gene-Disease associations (from GenCC):
  • intellectual disability, X-linked 58
    Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
  • non-syndromic X-linked intellectual disability
    Inheritance: XL Classification: MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004615.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
TSPAN7
NM_004615.4
MANE Select
c.43C>Gp.Leu15Val
missense
Exon 1 of 8NP_004606.2

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
TSPAN7
ENST00000378482.7
TSL:1 MANE Select
c.43C>Gp.Leu15Val
missense
Exon 1 of 8ENSP00000367743.2P41732
ENSG00000250349
ENST00000465127.1
TSL:5
c.172-104532C>G
intron
N/AENSP00000417050.1B4E171
TSPAN7
ENST00000286824.6
TSL:2
c.43C>Gp.Leu15Val
missense
Exon 1 of 9ENSP00000286824.6B4DDG0

Frequencies

GnomAD3 genomes
Cov.:
21
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.60
BayesDel_addAF
Benign
-0.0045
T
BayesDel_noAF
Benign
-0.24
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.12
T
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.86
D
M_CAP
Pathogenic
0.91
D
MetaRNN
Uncertain
0.57
D
MetaSVM
Benign
-0.51
T
MutationAssessor
Benign
1.2
L
PhyloP100
4.3
PrimateAI
Pathogenic
0.87
D
PROVEAN
Benign
-1.8
N
REVEL
Benign
0.17
Sift
Benign
0.15
T
Sift4G
Benign
0.17
T
Polyphen
0.099
B
Vest4
0.42
MutPred
0.65
Loss of catalytic residue at L15 (P = 0.0337)
MVP
0.75
MPC
2.0
ClinPred
0.56
D
GERP RS
4.9
PromoterAI
-0.0070
Neutral
Varity_R
0.48
gMVP
0.82
Mutation Taster
=211/89
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs2069111091; hg19: chrX-38420842; API