rs201047637

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_004615.4(TSPAN7):c.416G>A(p.Arg139Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000553 in 1,194,557 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 23 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R139W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.000059 ( 0 hom. 23 hem. )

Consequence

TSPAN7
NM_004615.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.763

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: G2P, Labcorp Genetics (formerly Invitae)
non-syndromic X-linked intellectual disability
Inheritance: XL Classification: MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet

TSPAN7 links:

ENSG00000250349 (HGNC:):

ENSG00000250349 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.021139175).

BS2

High Hemizygotes in GnomAdExome4 at 23 XL gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN7	NM_004615.4	MANE Select	c.416G>A	p.Arg139Gln	missense	Exon 4 of 8	NP_004606.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TSPAN7	ENST00000378482.7	TSL:1 MANE Select	c.416G>A	p.Arg139Gln	missense	Exon 4 of 8	ENSP00000367743.2
ENSG00000250349	ENST00000465127.1	TSL:5	c.506G>A	p.Arg169Gln	missense	Exon 6 of 9	ENSP00000417050.1
TSPAN7	ENST00000286824.6	TSL:2	c.467G>A	p.Arg156Gln	missense	Exon 5 of 9	ENSP00000286824.6

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111423

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000377

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000648

AC:

AN:

154352

AF XY:

0.000105

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000161

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000456

Gnomad OTH exome

AF:

0.000251

GnomAD4 exome

AF:

0.0000591

AC:

AN:

1083078

Hom.:

Cov.:

AF XY:

0.0000652

AC XY:

AN XY:

352674

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26212

American (AMR)

AF:

0.000149

AC:

AN:

33463

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19080

East Asian (EAS)

AF:

0.0000337

AC:

AN:

29662

South Asian (SAS)

AF:

0.0000579

AC:

AN:

51802

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39544

Middle Eastern (MID)

AF:

0.000245

AC:

AN:

4081

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

833712

Other (OTH)

AF:

0.000110

AC:

AN:

45522

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000179

AC:

AN:

111479

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33663

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30696

American (AMR)

AF:

0.00

AC:

AN:

10512

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2650

East Asian (EAS)

AF:

0.00

AC:

AN:

3541

South Asian (SAS)

AF:

0.00

AC:

AN:

2620

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6025

Middle Eastern (MID)

AF:

0.00

AC:

AN:

214

European-Non Finnish (NFE)

AF:

0.0000377

AC:

AN:

53034

Other (OTH)

AF:

0.00

AC:

AN:

1506

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000296

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000250

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:2

Apr 29, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.416G>A (p.R139Q) alteration is located in exon 4 (coding exon 4) of the TSPAN7 gene. This alteration results from a G to A substitution at nucleotide position 416, causing the arginine (R) at amino acid position 139 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

Apr 05, 2017

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.15

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.76

M_CAP

Benign

0.057

MetaRNN

Benign

0.021

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.77

PhyloP100

0.76

PrimateAI

Benign

0.27

PROVEAN

Benign

0.77

REVEL

Benign

0.13

Sift

Benign

0.74

Sift4G

Benign

0.85

Polyphen

0.0

Vest4

0.11

MVP

0.39

MPC

0.69

ClinPred

0.042

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.061

gMVP

0.39

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over