11-44909745-T-C

Position:

• chr11-44909745-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_130783.5(TSPAN18):​c.104T>C​(p.Met35Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TSPAN18 NM_130783.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.21

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17988235).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPAN18	NM_130783.5	c.104T>C	p.Met35Thr	missense_variant	5/10	ENST00000520358.7	NP_570139.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPAN18	ENST00000520358.7	c.104T>C	p.Met35Thr	missense_variant	5/10	5	NM_130783.5	ENSP00000429993	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Feb 13, 2024

The c.104T>C (p.M35T) alteration is located in exon 4 (coding exon 2) of the TSPAN18 gene. This alteration results from a T to C substitution at nucleotide position 104, causing the methionine (M) at amino acid position 35 to be replaced by a threonine (T). 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	0.18
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.093	.;.;T;.;T;.
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.0075
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.78	T;T;T;T;.;T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.18	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.82	.;.;L;.;L;.
MutationTaster	Benign	0.88	N;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.68	N;N;N;N;N;N
REVEL	Benign	0.16
Sift	Benign	0.080	T;T;D;T;D;T
Sift4G	Benign	0.70	T;T;T;T;T;T
Polyphen		0.059	.;.;B;.;B;.
Vest4		0.60
MutPred		0.49		Gain of glycosylation at M35 (P = 0.0105);Gain of glycosylation at M35 (P = 0.0105);Gain of glycosylation at M35 (P = 0.0105);.;Gain of glycosylation at M35 (P = 0.0105);.;
MVP		0.12
MPC		0.39
ClinPred		0.51	D
GERP RS		3.8
Varity_R		0.11
gMVP		0.44

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: chr11-44931296;