X-38675725-G-C

Position:

• chrX-38675725-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004615.4(TSPAN7):​c.462G>C​(p.Gln154His) 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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: TSPAN7 NM_004615.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.48

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31767756).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPAN7	NM_004615.4	c.462G>C	p.Gln154His	missense_variant	5/8	ENST00000378482.7	NP_004606.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPAN7	ENST00000378482.7	c.462G>C	p.Gln154His	missense_variant	5/8	1	NM_004615.4	ENSP00000367743	P1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2021

Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27535533) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	.;T;.
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.74	T;T;T
M_CAP	Pathogenic	0.53	D
MetaRNN	Benign	0.32	T;T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	-0.22	.;N;.
MutationTaster	Benign	0.99	D;D;D;D
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.36	N;N;N
REVEL	Benign	0.22
Sift	Benign	0.27	T;T;T
Sift4G	Benign	0.38	T;T;T
Polyphen		0.0020, 0.0050	.;B;B
Vest4		0.34
MVP		0.53
MPC		0.60
ClinPred		0.87	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.36
gMVP		0.71

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-38534979;