X-100635229-A-G

Variant names:

• chrX-100635229-A-G
• rs141301339
• NM_003270.4:c.300T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_003270.4(TSPAN6):​c.300T>C​(p.Val100Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000185 in 1,196,235 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 53 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 0.00092 (0 hom., 24 hem., cov: 24)
  • Exomes 𝑓: 0.00011 (0 hom. 29 hem.)
• Consequence: TSPAN6 NM_003270.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.226
• Publications: 0 publications found

Genes affected

TSPAN6 (HGNC:11858): (tetraspanin 6) 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. The protein encoded by this gene is a cell surface glycoprotein and is highly similar in sequence to the transmembrane 4 superfamily member 2 protein. It functions as a negative regulator of retinoic acid-inducible gene I-like receptor-mediated immune signaling via its interaction with the mitochondrial antiviral signaling-centered signalosome. This gene uses alternative polyadenylation sites, and multiple transcript variants result from alternative splicing. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant X-100635229-A-G is Benign according to our data. Variant chrX-100635229-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2661034.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.226 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 24 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPAN6	NM_003270.4	c.300T>C	p.Val100Val	synonymous_variant	Exon 3 of 8	ENST00000373020.9	NP_003261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPAN6	ENST00000373020.9	c.300T>C	p.Val100Val	synonymous_variant	Exon 3 of 8	1	NM_003270.4	ENSP00000362111.4
TSPAN6	ENST00000612152.4	c.36T>C	p.Val12Val	synonymous_variant	Exon 3 of 7	5		ENSP00000482130.1
TSPAN6	ENST00000494424.1	n.572T>C		non_coding_transcript_exon_variant	Exon 4 of 6	2
TSPAN6	ENST00000496771.5	n.712T>C		non_coding_transcript_exon_variant	Exon 3 of 6	3

Frequencies

GnomAD3 genomes AF: 0.000923 AC: 104 AN: 112676 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00313

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000472

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: 0.00

Gnomad OTH AF: 0.00132

GnomAD2 exomes AF: 0.000223 AC: 36 AN: 161222 AF XY: 0.000172

Gnomad AFR exome AF: 0.00264

Gnomad AMR exome AF: 0.000151

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000482

GnomAD4 exome AF: 0.000108 AC: 117 AN: 1083504 Hom.: 0 Cov.: 28 AF XY: 0.0000821 AC XY: 29 AN XY: 353186

African (AFR) AF: 0.00340 AC: 87 AN: 25625

American (AMR) AF: 0.000375 AC: 13 AN: 34698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19236

East Asian (EAS) AF: 0.00 AC: 0 AN: 29061

South Asian (SAS) AF: 0.00 AC: 0 AN: 51697

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40004

Middle Eastern (MID) AF: 0.000485 AC: 2 AN: 4122

European-Non Finnish (NFE) AF: 0.00000360 AC: 3 AN: 833524

Other (OTH) AF: 0.000264 AC: 12 AN: 45537

GnomAD4 genome AF: 0.000923 AC: 104 AN: 112731 Hom.: 0 Cov.: 24 AF XY: 0.000688 AC XY: 24 AN XY: 34869

African (AFR) AF: 0.00312 AC: 97 AN: 31088

American (AMR) AF: 0.000471 AC: 5 AN: 10611

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2659

East Asian (EAS) AF: 0.00 AC: 0 AN: 3595

South Asian (SAS) AF: 0.00 AC: 0 AN: 2740

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6197

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53401

Other (OTH) AF: 0.00130 AC: 2 AN: 1537

Alfa AF: 0.000260 Hom.: 2

Bravo AF: 0.00104

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TSPAN6: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	10
DANN	Benign	0.75
PhyloP100		0.23
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
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: rs141301339; hg19: chrX-99890226;