chr10-80517959-G-A

Position:

• chr10-80517959-G-A

Variant summary

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

The NM_030927.4(TSPAN14):​c.796G>A​(p.Ala266Thr) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TSPAN14 NM_030927.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.09

Genes affected

TSPAN14 (HGNC:23303): (tetraspanin 14) Enables enzyme binding activity. Involved in positive regulation of Notch signaling pathway; protein localization to plasma membrane; and protein maturation. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TSPAN14 (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=0.1841613).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPAN14	NM_030927.4	c.796G>A	p.Ala266Thr	missense_variant	9/9	ENST00000429989.8	NP_112189.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPAN14	ENST00000429989.8	c.796G>A	p.Ala266Thr	missense_variant	9/9	1	NM_030927.4	ENSP00000396270.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1410336 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 696472

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ESP6500AA AF: 0.000228 AC: 1

ESP6500EA AF: 0.00 AC: 0

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 05, 2024

The c.796G>A (p.A266T) alteration is located in exon 9 (coding exon 8) of the TSPAN14 gene. This alteration results from a G to A substitution at nucleotide position 796, causing the alanine (A) at amino acid position 266 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	0.15
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.065	T;.;.;T;T;T;.
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.93	.;D;.;.;D;D;D
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.18	T;T;T;T;T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.9	L;.;.;L;.;L;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-2.3	N;N;N;N;N;N;.
REVEL	Benign	0.13
Sift	Uncertain	0.0030	D;D;D;D;D;D;.
Sift4G	Uncertain	0.0090	D;D;D;D;D;D;D
Polyphen		0.95	P;.;D;P;.;P;D
Vest4		0.078
MVP		0.21
MPC		0.80
ClinPred		0.84	D
GERP RS		4.8
Varity_R		0.17
gMVP		0.82

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

LitVar

Other links and lift over

dbSNP: rs374281205; hg19: chr10-82277715; COSMIC: COSV99627837; COSMIC: COSV99627837;