Genetic Variant TSPAN7:p.Asp126Asp (chrX-38674253-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_004615.4(TSPAN7):c.378C>T(p.Asp126Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000934 in 1,198,898 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 28 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., 11 hem., cov: 22)

Exomes 𝑓: 0.000064 ( 0 hom. 17 hem. )

Consequence

TSPAN7
NM_004615.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.900

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: Labcorp Genetics (formerly Invitae), G2P
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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BP6

Variant X-38674253-C-T is Benign according to our data. Variant chrX-38674253-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3042930.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.9 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 11 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN7	NM_004615.4	MANE Select	c.378C>T	p.Asp126Asp	synonymous	Exon 4 of 8	NP_004606.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TSPAN7	ENST00000378482.7	TSL:1 MANE Select	c.378C>T	p.Asp126Asp	synonymous	Exon 4 of 8	ENSP00000367743.2	P41732
ENSG00000250349	ENST00000465127.1	TSL:5	c.468C>T	p.Asp156Asp	synonymous	Exon 6 of 9	ENSP00000417050.1	B4E171
TSPAN7	ENST00000286824.6	TSL:2	c.429C>T	p.Asp143Asp	synonymous	Exon 5 of 9	ENSP00000286824.6	B4DDG0

Frequencies

GnomAD3 genomes

AF:

0.000377

AC:

AN:

111534

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00108

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000950

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000282

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000113

Gnomad OTH

AF:

0.000668

GnomAD2 exomes

AF:

0.000162

AC:

AN:

160475

AF XY:

0.0000793

show subpopulations

Gnomad AFR exome

AF:

0.00156

Gnomad AMR exome

AF:

0.000117

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000578

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000644

AC:

AN:

1087309

Hom.:

Cov.:

AF XY:

0.0000478

AC XY:

AN XY:

355503

show subpopulations

African (AFR)

AF:

0.000913

AC:

AN:

26274

American (AMR)

AF:

0.000117

AC:

AN:

34057

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19150

East Asian (EAS)

AF:

0.00

AC:

AN:

29882

South Asian (SAS)

AF:

0.0000192

AC:

AN:

52137

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39843

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4099

European-Non Finnish (NFE)

AF:

0.0000419

AC:

AN:

836193

Other (OTH)

AF:

0.000131

AC:

AN:

45674

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

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:

0.000376

AC:

AN:

111589

Hom.:

Cov.:

AF XY:

0.000326

AC XY:

AN XY:

33763

show subpopulations

African (AFR)

AF:

0.00107

AC:

AN:

30704

American (AMR)

AF:

0.0000949

AC:

AN:

10540

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2649

East Asian (EAS)

AF:

0.000282

AC:

AN:

3540

South Asian (SAS)

AF:

0.00

AC:

AN:

2622

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6032

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.000113

AC:

AN:

53083

Other (OTH)

AF:

0.000660

AC:

AN:

1516

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.000270

Hom.:

Bravo

AF:

0.000295

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

TSPAN7-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

0.23

(source)

DANN

Benign

0.64

PhyloP100

-0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=88/12

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over