11-44919272-C-G

Position:

• chr11-44919272-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_130783.5(TSPAN18):​c.392C>G​(p.Thr131Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TSPAN18 NM_130783.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.79

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]

TSPAN18 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPAN18	NM_130783.5	c.392C>G	p.Thr131Arg	missense_variant	7/10	ENST00000520358.7	NP_570139.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPAN18	ENST00000520358.7	c.392C>G	p.Thr131Arg	missense_variant	7/10	5	NM_130783.5	ENSP00000429993.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 19, 2024

The c.392C>G (p.T131R) alteration is located in exon 6 (coding exon 4) of the TSPAN18 gene. This alteration results from a C to G substitution at nucleotide position 392, causing the threonine (T) at amino acid position 131 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	.;T;T;.;T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.92	D;D;D;D;.
M_CAP	Uncertain	0.088	D
MetaRNN	Uncertain	0.72	D;D;D;D;D
MetaSVM	Uncertain	-0.072	T
MutationAssessor	Uncertain	2.2	.;.;M;.;M
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.3	N;N;N;N;N
REVEL	Uncertain	0.58
Sift	Benign	0.061	T;D;T;T;T
Sift4G	Benign	0.16	T;D;T;T;T
Polyphen		0.91	.;.;P;.;P
Vest4		0.50, 0.50
MutPred		0.70		Gain of solvent accessibility (P = 0.0456);.;Gain of solvent accessibility (P = 0.0456);.;Gain of solvent accessibility (P = 0.0456);
MVP		0.68
MPC		0.85
ClinPred		0.92	D
GERP RS		4.3
Varity_R		0.30
gMVP		0.81

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-44940823;