12-3201253-C-G

Position:

• chr12-3201253-C-G

Variant summary

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

The NM_006675.5(TSPAN9):​c.60C>G​(p.Phe20Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TSPAN9 NM_006675.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.69

Genes affected

TSPAN9 (HGNC:21640): (tetraspanin 9) 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. Alternatively spliced transcripts encoding the same protein have been identified. [provided by RefSeq, Nov 2009]

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
TSPAN9	NM_006675.5	c.60C>G	p.Phe20Leu	missense_variant	3/9	ENST00000011898.10	NP_006666.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPAN9	ENST00000011898.10	c.60C>G	p.Phe20Leu	missense_variant	3/9	1	NM_006675.5	ENSP00000011898.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

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

Mar 22, 2023

The c.60C>G (p.F20L) alteration is located in exon 3 (coding exon 1) of the TSPAN9 gene. This alteration results from a C to G substitution at nucleotide position 60, causing the phenylalanine (F) at amino acid position 20 to be replaced by a leucine (L). 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	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.43	T;T;.;T
Eigen	Benign	0.060
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.81	T;.;D;T
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.72	D;D;D;D
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Benign	1.9	M;M;.;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-3.6	D;D;.;D
REVEL	Pathogenic	0.65
Sift	Uncertain	0.0090	D;D;.;D
Sift4G	Benign	0.10	T;T;.;T
Polyphen		0.0090	B;B;.;.
Vest4		0.89
MutPred		0.66		Gain of catalytic residue at G24 (P = 5e-04);Gain of catalytic residue at G24 (P = 5e-04);.;Gain of catalytic residue at G24 (P = 5e-04);
MVP		0.98
MPC		0.64
ClinPred		0.97	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.40
gMVP		0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr12-3310419;