NM_003270.4:c.396G>A

Variant names:

• chrX-100633985-C-T
• rs189159745
• NM_003270.4:c.396G>A

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.396G>A​(p.Gln132Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000447 in 1,200,208 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 181 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00033 (0 hom., 17 hem., cov: 21)
  • Exomes 𝑓: 0.00046 (0 hom. 164 hem.)
• Consequence: TSPAN6 NM_003270.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.86
• 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=-0.75).
• BP6: Variant X-100633985-C-T is Benign according to our data. Variant chrX-100633985-C-T is described in ClinVar as [Benign]. Clinvar id is 742141.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.87 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 17 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPAN6	NM_003270.4	c.396G>A	p.Gln132Gln	synonymous_variant	Exon 4 of 8	ENST00000373020.9	NP_003261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPAN6	ENST00000373020.9	c.396G>A	p.Gln132Gln	synonymous_variant	Exon 4 of 8	1	NM_003270.4	ENSP00000362111.4
TSPAN6	ENST00000612152.4	c.132G>A	p.Gln44Gln	synonymous_variant	Exon 4 of 7	5		ENSP00000482130.1
TSPAN6	ENST00000494424.1	n.668G>A		non_coding_transcript_exon_variant	Exon 5 of 6	2
TSPAN6	ENST00000496771.5	n.808G>A		non_coding_transcript_exon_variant	Exon 4 of 6	3

Frequencies

GnomAD3 genomes AF: 0.000330 AC: 36 AN: 109227 Hom.: 0 Cov.: 21

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: 0.00393

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000266

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000638 AC: 116 AN: 181959 AF XY: 0.000541

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00539

Gnomad NFE exome AF: 0.000404

Gnomad OTH exome AF: 0.000222

GnomAD4 exome AF: 0.000459 AC: 501 AN: 1090928 Hom.: 0 Cov.: 27 AF XY: 0.000460 AC XY: 164 AN XY: 356858

African (AFR) AF: 0.00 AC: 0 AN: 26296

American (AMR) AF: 0.00 AC: 0 AN: 35174

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19334

East Asian (EAS) AF: 0.00 AC: 0 AN: 30159

South Asian (SAS) AF: 0.00 AC: 0 AN: 53904

European-Finnish (FIN) AF: 0.00518 AC: 206 AN: 39740

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4123

European-Non Finnish (NFE) AF: 0.000347 AC: 290 AN: 836326

Other (OTH) AF: 0.000109 AC: 5 AN: 45872

GnomAD4 genome AF: 0.000329 AC: 36 AN: 109280 Hom.: 0 Cov.: 21 AF XY: 0.000539 AC XY: 17 AN XY: 31542

African (AFR) AF: 0.00 AC: 0 AN: 30055

American (AMR) AF: 0.00 AC: 0 AN: 9963

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2622

East Asian (EAS) AF: 0.00 AC: 0 AN: 3497

South Asian (SAS) AF: 0.00 AC: 0 AN: 2481

European-Finnish (FIN) AF: 0.00393 AC: 22 AN: 5596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 214

European-Non Finnish (NFE) AF: 0.000266 AC: 14 AN: 52688

Other (OTH) AF: 0.00 AC: 0 AN: 1480

Alfa AF: 0.000291 Hom.: 3

Bravo AF: 0.000155

EpiCase AF: 0.000219

EpiControl AF: 0.000653

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 02, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.3
DANN	Benign	0.39
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs189159745; hg19: chrX-99888982;