1-46181108-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 8P and 6B. PVS1 BP6_Moderate BS2

The NM_005727.4(TSPAN1):c.1A>G(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.000564 in 1,613,934 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00061 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00056 (6 hom.)
• Consequence: TSPAN1 NM_005727.4 start_lost
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.32

Genes affected

TSPAN1 (HGNC:20657): (tetraspanin 1) 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. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PVS1: Start lost variant, no new inframe start found.
• BP6: Variant 1-46181108-A-G is Benign according to our data. Variant chr1-46181108-A-G is described in ClinVar as [Benign]. Clinvar id is 725095.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSPAN1	NM_005727.4	c.1A>G	p.Met1?	start_lost	3/9	ENST00000372003.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSPAN1	ENST00000372003.6	c.1A>G	p.Met1?	start_lost	3/9	1	NM_005727.4	P1

Frequencies

GnomAD3 genomes AF: 0.000611 AC: 93 AN: 152174 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0121

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.00134 AC: 336 AN: 251102 Hom.: 4 AF XY: 0.00125 AC XY: 170 AN XY: 135702

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0150

Gnomad SAS exome AF: 0.000556

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000211

Gnomad OTH exome AF: 0.000817

GnomAD4 exome AF: 0.000560 AC: 818 AN: 1461642 Hom.: 6 Cov.: 31 AF XY: 0.000554 AC XY: 403 AN XY: 727126

Gnomad4 AFR exome AF: 0.0000896

Gnomad4 AMR exome AF: 0.000291

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0110

Gnomad4 SAS exome AF: 0.000499

Gnomad4 FIN exome AF: 0.0000749

Gnomad4 NFE exome AF: 0.000204

Gnomad4 OTH exome AF: 0.00147

GnomAD4 genome AF: 0.000611 AC: 93 AN: 152292 Hom.: 2 Cov.: 32 AF XY: 0.000604 AC XY: 45 AN XY: 74466

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.000392

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0121

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.000720 Hom.: 1

Bravo AF: 0.000714

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00149 AC: 181

Asia WGS AF: 0.00779 AC: 27 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.10
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	1.0	D
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.45
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.53
MVP		0.37
ClinPred		0.094	T
GERP RS		4.9
Varity_R		0.84
gMVP		0.82

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

LitVar

Other links and lift over

dbSNP: rs2234266; hg19: chr1-46646780;