15-77052890-T-C

Position:

• chr15-77052890-T-C

Variant summary

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

The ENST00000267970.9(TSPAN3):​c.472A>G​(p.Asn158Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: TSPAN3 ENST00000267970.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.23

Genes affected

TSPAN3 (HGNC:17752): (tetraspanin 3) 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 use of alternate polyadenylation sites has been found for this gene. Multiple alternative transcripts encoding different isoforms have been described. [provided by RefSeq, Dec 2009]

TSPAN3 (HGNC:):

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=0.23532847).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPAN3	NM_005724.6	c.472A>G	p.Asn158Asp	missense_variant	5/7	ENST00000267970.9	NP_005715.1
TSPAN3	NM_198902.3	c.397A>G	p.Asn133Asp	missense_variant	4/6		NP_944492.1
TSPAN3	NM_001168412.2	c.280A>G	p.Asn94Asp	missense_variant	4/6		NP_001161884.1
TSPAN3	XM_017021857.2	c.355A>G	p.Asn119Asp	missense_variant	5/7		XP_016877346.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPAN3	ENST00000267970.9	c.472A>G	p.Asn158Asp	missense_variant	5/7	1	NM_005724.6	ENSP00000267970.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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

May 14, 2024

The c.472A>G (p.N158D) alteration is located in exon 5 (coding exon 5) of the TSPAN3 gene. This alteration results from a A to G substitution at nucleotide position 472, causing the asparagine (N) at amino acid position 158 to be replaced by an aspartic acid (D). 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	0.11
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;.;.;T
Eigen	Benign	-0.064
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.79	T;T;T;T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.24	T;T;T;T
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	1.4	L;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.9	N;N;N;N
REVEL	Uncertain	0.30
Sift	Benign	0.36	T;T;T;T
Sift4G	Benign	0.67	T;T;T;T
Polyphen		0.028	B;.;.;.
Vest4		0.19
MutPred		0.47		Gain of ubiquitination at K163 (P = 0.1536);.;.;.;
MVP		0.51
MPC		0.77
ClinPred		0.69	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.32
gMVP		0.78

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: chr15-77345232;