NM_004615.4:c.441C>T

Variant names:

• chrX-38674316-C-T
• rs111440990
• NM_004615.4:c.441C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004615.4(TSPAN7):​c.441C>T​(p.Ser147Ser) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00732 in 1,180,950 control chromosomes in the GnomAD database, including 294 homozygotes. There are 2,347 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (143 hom., 978 hem., cov: 22)
  • Exomes 𝑓: 0.0046 (151 hom. 1369 hem.)
• Consequence: TSPAN7 NM_004615.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.0001334
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.20
• Publications: 2 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant X-38674316-C-T is Benign according to our data. Variant chrX-38674316-C-T is described in ClinVar as Benign. ClinVar VariationId is 130645.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.2 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

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.441C>T	p.Ser147Ser	splice_region synonymous	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.441C>T	p.Ser147Ser	splice_region synonymous	Exon 4 of 8	ENSP00000367743.2	P41732
	ENSG00000250349	ENST00000465127.1	TSL:5	c.531C>T	p.Ser177Ser	splice_region synonymous	Exon 6 of 9	ENSP00000417050.1	B4E171
	TSPAN7	ENST00000286824.6	TSL:2	c.492C>T	p.Ser164Ser	splice_region synonymous	Exon 5 of 9	ENSP00000286824.6	B4DDG0

Frequencies

GnomAD3 genomes AF: 0.0336 AC: 3736 AN: 111063 Hom.: 144 Cov.: 22

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0175

Gnomad ASJ AF: 0.00227

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000167

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00145

Gnomad OTH AF: 0.0228

GnomAD2 exomes AF: 0.00985 AC: 1392 AN: 141252 AF XY: 0.00672

Gnomad AFR exome AF: 0.113

Gnomad AMR exome AF: 0.00697

Gnomad ASJ exome AF: 0.00237

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00126

Gnomad OTH exome AF: 0.00559

GnomAD4 exome AF: 0.00457 AC: 4894 AN: 1069833 Hom.: 151 Cov.: 29 AF XY: 0.00397 AC XY: 1369 AN XY: 344597

African (AFR) AF: 0.118 AC: 3042 AN: 25873

American (AMR) AF: 0.00776 AC: 247 AN: 31819

Ashkenazi Jewish (ASJ) AF: 0.00185 AC: 35 AN: 18907

East Asian (EAS) AF: 0.00 AC: 0 AN: 29112

South Asian (SAS) AF: 0.000392 AC: 20 AN: 51005

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38938

Middle Eastern (MID) AF: 0.00694 AC: 28 AN: 4034

European-Non Finnish (NFE) AF: 0.00122 AC: 1008 AN: 825125

Other (OTH) AF: 0.0114 AC: 514 AN: 45020

GnomAD4 genome AF: 0.0338 AC: 3753 AN: 111117 Hom.: 143 Cov.: 22 AF XY: 0.0293 AC XY: 978 AN XY: 33333

African (AFR) AF: 0.113 AC: 3452 AN: 30473

American (AMR) AF: 0.0175 AC: 183 AN: 10476

Ashkenazi Jewish (ASJ) AF: 0.00227 AC: 6 AN: 2643

East Asian (EAS) AF: 0.00 AC: 0 AN: 3527

South Asian (SAS) AF: 0.00 AC: 0 AN: 2600

European-Finnish (FIN) AF: 0.000167 AC: 1 AN: 5995

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.00145 AC: 77 AN: 52989

Other (OTH) AF: 0.0225 AC: 34 AN: 1508

Alfa AF: 0.0121 Hom.: 582

Bravo AF: 0.0396

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	2.4
DANN	Benign	0.58
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=79/21	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00013
dbscSNV1_RF	Benign	0.034
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

dbSNP: rs111440990; hg19: chrX-38533570;