11-44919277-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_130783.5(TSPAN18):c.397G>A(p.Val133Ile) variant causes a missense change. The variant allele was found at a frequency of 0.363 in 1,613,394 control chromosomes in the GnomAD database, including 112,083 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.29 (7998 hom., cov: 32)
  • Exomes 𝑓: 0.37 (104085 hom.)
• Consequence: TSPAN18 NM_130783.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.73

Genes affected

TSPAN18 (HGNC:20660): (tetraspanin 18) Predicted to be integral component of membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TP53I11 (HGNC:16842): (tumor protein p53 inducible protein 11) Predicted to be involved in negative regulation of cell population proliferation. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.376007E-4).
• BP6: Variant 11-44919277-G-A is Benign according to our data. Variant chr11-44919277-G-A is described in ClinVar as [Benign]. Clinvar id is 3059513.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSPAN18	NM_130783.5	c.397G>A	p.Val133Ile	missense_variant	7/10	ENST00000520358.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSPAN18	ENST00000520358.7	c.397G>A	p.Val133Ile	missense_variant	7/10	5	NM_130783.5	P1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44593 AN: 151990 Hom.: 8001 Cov.: 32

Gnomad AFR AF: 0.0881

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.474

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.299

GnomAD3 exomes AF: 0.375 AC: 94359 AN: 251362 Hom.: 19384 AF XY: 0.378 AC XY: 51332 AN XY: 135840

Gnomad AFR exome AF: 0.0836

Gnomad AMR exome AF: 0.436

Gnomad ASJ exome AF: 0.223

Gnomad EAS exome AF: 0.594

Gnomad SAS exome AF: 0.461

Gnomad FIN exome AF: 0.354

Gnomad NFE exome AF: 0.359

Gnomad OTH exome AF: 0.354

GnomAD4 exome AF: 0.370 AC: 541168 AN: 1461286 Hom.: 104085 Cov.: 39 AF XY: 0.372 AC XY: 270470 AN XY: 726972

Gnomad4 AFR exome AF: 0.0733

Gnomad4 AMR exome AF: 0.432

Gnomad4 ASJ exome AF: 0.227

Gnomad4 EAS exome AF: 0.576

Gnomad4 SAS exome AF: 0.449

Gnomad4 FIN exome AF: 0.353

Gnomad4 NFE exome AF: 0.369

Gnomad4 OTH exome AF: 0.355

GnomAD4 genome AF: 0.293 AC: 44588 AN: 152108 Hom.: 7998 Cov.: 32 AF XY: 0.299 AC XY: 22219 AN XY: 74334

Gnomad4 AFR AF: 0.0878

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.582

Gnomad4 SAS AF: 0.473

Gnomad4 FIN AF: 0.353

Gnomad4 NFE AF: 0.358

Gnomad4 OTH AF: 0.302

Alfa AF: 0.344 Hom.: 23699

Bravo AF: 0.285

TwinsUK AF: 0.385 AC: 1428

ALSPAC AF: 0.374 AC: 1440

ESP6500AA AF: 0.0999 AC: 440

ESP6500EA AF: 0.342 AC: 2937

ExAC AF: 0.370 AC: 44901

Asia WGS AF: 0.497 AC: 1726 AN: 3478

EpiCase AF: 0.335

EpiControl AF: 0.338

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

TSPAN18-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.34
Cadd	Benign	18
Dann	Uncertain	0.98
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.83	T;T;T;T;.
MetaRNN	Benign	0.00034	T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationTaster	Benign	0.00074	P;P
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.48	N;N;N;N;N
REVEL	Benign	0.19
Sift	Benign	0.28	T;T;T;T;T
Sift4G	Benign	0.32	T;T;T;T;T
Polyphen		0.36	.;.;B;.;B
Vest4		0.053, 0.054
MPC		0.27
ClinPred		0.0042	T
GERP RS		2.4
Varity_R		0.073
gMVP		0.56

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: rs2291334; hg19: chr11-44940828; COSMIC: COSV60885942; COSMIC: COSV60885942;