chrX-38561589-C-T

Variant names:

• chrX-38561589-C-T
• NM_004615.4:c.43C>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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.32

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]

ENSG00000250349 (HGNC:):

ACMG classification

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
TSPAN7	NM_004615.4	c.43C>T	p.Leu15Phe	missense_variant	Exon 1 of 8	ENST00000378482.7	NP_004606.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPAN7	ENST00000378482.7	c.43C>T	p.Leu15Phe	missense_variant	Exon 1 of 8	1	NM_004615.4	ENSP00000367743.2
ENSG00000250349	ENST00000465127.1	c.172-104532C>T		intron_variant	Intron 3 of 8	5		ENSP00000417050.1

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

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;