19-11301235-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001282509.2(TSPAN16):c.377C>T(p.Thr126Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,613,744 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
TSPAN16
NM_001282509.2 missense
NM_001282509.2 missense
Scores
1
6
8
Clinical Significance
Conservation
PhyloP100: 1.60
Genes affected
TSPAN16 (HGNC:30725): (tetraspanin 16) 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. This encoded protein might couple to signal transduction pathways and possibly modulate cellular activation and adhesion in haemopoietic and neural tissue. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]
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ACMG classification
Classification made for transcript
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 | UniProt |
---|---|---|---|---|---|---|---|
TSPAN16 | NM_001282509.2 | c.377C>T | p.Thr126Ile | missense_variant | 4/7 | ENST00000590327.6 | |
HSPC102 | XR_936316.2 | n.140G>A | splice_region_variant, non_coding_transcript_exon_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSPAN16 | ENST00000590327.6 | c.377C>T | p.Thr126Ile | missense_variant | 4/7 | 2 | NM_001282509.2 | P1 | |
ENST00000686945.1 | n.105-4809G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151908Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251484Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135914
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GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461836Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727222
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GnomAD4 genome AF: 0.00000658 AC: 1AN: 151908Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74156
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 27, 2023 | The c.377C>T (p.T126I) alteration is located in exon 4 (coding exon 4) of the TSPAN16 gene. This alteration results from a C to T substitution at nucleotide position 377, causing the threonine (T) at amino acid position 126 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;T
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Benign
L;L;.;L
MutationTaster
Benign
N;N;N
PrimateAI
Uncertain
T
Sift4G
Pathogenic
D;T;T;T
Polyphen
0.82
.;P;.;.
Vest4
MutPred
Gain of methylation at K129 (P = 0.0402);Gain of methylation at K129 (P = 0.0402);.;Gain of methylation at K129 (P = 0.0402);
MVP
MPC
0.36
ClinPred
D
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at