NM_004615.4:c.389C>T

Variant names:

• chrX-38674264-C-T
• NM_004615.4:c.389C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004615.4(TSPAN7):​c.389C>T​(p.Thr130Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000919 in 1,087,608 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.2e-7 (0 hom. 0 hem.)
• Consequence: TSPAN7 NM_004615.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.94
• Publications: 0 publications found

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

ENSG00000250349 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21610752).

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.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN7	NM_004615.4	MANE Select	c.389C>T	p.Thr130Ile	missense	Exon 4 of 8	NP_004606.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN7	ENST00000378482.7	TSL:1 MANE Select	c.389C>T	p.Thr130Ile	missense	Exon 4 of 8	ENSP00000367743.2	P41732
	ENSG00000250349	ENST00000465127.1	TSL:5	c.479C>T	p.Thr160Ile	missense	Exon 6 of 9	ENSP00000417050.1	B4E171
	TSPAN7	ENST00000286824.6	TSL:2	c.440C>T	p.Thr147Ile	missense	Exon 5 of 9	ENSP00000286824.6	B4DDG0

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 9.19e-7 AC: 1 AN: 1087608 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 355686

African (AFR) AF: 0.00 AC: 0 AN: 26277

American (AMR) AF: 0.00 AC: 0 AN: 34082

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19152

East Asian (EAS) AF: 0.00 AC: 0 AN: 29879

South Asian (SAS) AF: 0.00 AC: 0 AN: 52161

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39831

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4098

European-Non Finnish (NFE) AF: 0.00000120 AC: 1 AN: 836431

Other (OTH) AF: 0.00 AC: 0 AN: 45697

GnomAD4 genome Cov.: 22

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.31	T
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.78	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	0.97	L
PhyloP100		3.9
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.29
Sift	Benign	0.089	T
Sift4G	Benign	0.062	T
Polyphen		0.0050	B
Vest4		0.33
MVP		0.30
MPC		0.73
ClinPred		0.43	T
GERP RS		3.5
Varity_R		0.20
gMVP		0.60
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

hg19: chrX-38533518;