chrX-38561589-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004615.4(TSPAN7):​c.43C>T​(p.Leu15Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 21)

Consequence

TSPAN7
NM_004615.4 missense

Scores

3
7
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.32
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TSPAN7NM_004615.4 linkc.43C>T p.Leu15Phe missense_variant Exon 1 of 8 ENST00000378482.7 NP_004606.2 P41732

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TSPAN7ENST00000378482.7 linkc.43C>T p.Leu15Phe missense_variant Exon 1 of 8 1 NM_004615.4 ENSP00000367743.2 P41732
ENSG00000250349ENST00000465127.1 linkc.172-104532C>T intron_variant Intron 3 of 8 5 ENSP00000417050.1 B4E171

Frequencies

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

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 05, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.43C>T (p.L15F) alteration is located in exon 1 (coding exon 1) of the TSPAN7 gene. This alteration results from a C to T substitution at nucleotide position 43, causing the leucine (L) at amino acid position 15 to be replaced by a phenylalanine (F). 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
0.72
BayesDel_addAF
Uncertain
0.059
T
BayesDel_noAF
Benign
-0.15
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.34
T;.
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.74
T;T
M_CAP
Pathogenic
0.90
D
MetaRNN
Uncertain
0.59
D;D
MetaSVM
Uncertain
-0.12
T
MutationAssessor
Uncertain
2.2
M;.
PrimateAI
Pathogenic
0.89
D
PROVEAN
Uncertain
-2.4
N;N
REVEL
Benign
0.27
Sift
Benign
0.27
T;T
Sift4G
Benign
0.20
T;T
Polyphen
0.025
B;B
Vest4
0.46
MutPred
0.63
Loss of catalytic residue at L15 (P = 0.0018);Loss of catalytic residue at L15 (P = 0.0018);
MVP
0.89
MPC
1.9
ClinPred
0.87
D
GERP RS
4.9
Varity_R
0.49
gMVP
0.84

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: chrX-38420842; API