12-30963928-A-T

Position:

• chr12-30963928-A-T

Variant summary

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

The NM_001370302.1(TSPAN11):​c.187A>T​(p.Ile63Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,634 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: TSPAN11 NM_001370302.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.91

Genes affected

TSPAN11 (HGNC:30795): (tetraspanin 11) Predicted to be involved in cell migration. Predicted to be integral component of membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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
TSPAN11	NM_001370302.1	c.187A>T	p.Ile63Phe	missense_variant	3/8	ENST00000546076.6	NP_001357231.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPAN11	ENST00000546076.6	c.187A>T	p.Ile63Phe	missense_variant	3/8	2	NM_001370302.1	ENSP00000437403	P1
TSPAN11	ENST00000261177.10	c.187A>T	p.Ile63Phe	missense_variant	3/8	1		ENSP00000261177	P1
TSPAN11	ENST00000535215.5	c.-27A>T		5_prime_UTR_variant	2/7	2		ENSP00000445503

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461634 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727142

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: 0.00000270

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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

Dec 16, 2023

The c.187A>T (p.I63F) alteration is located in exon 3 (coding exon 2) of the TSPAN11 gene. This alteration results from a A to T substitution at nucleotide position 187, causing the isoleucine (I) at amino acid position 63 to be replaced by a phenylalanine (F). 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	Uncertain	0.39
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.33	T;T
Eigen	Benign	-0.045
Eigen_PC	Benign	-0.013
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	.;D
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.68	D;D
MetaSVM	Benign	-0.44	T
MutationAssessor	Uncertain	2.2	M;M
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.7	D;D
REVEL	Uncertain	0.55
Sift	Benign	0.075	T;T
Sift4G	Benign	0.064	T;T
Polyphen		0.12	B;B
Vest4		0.80
MutPred		0.63		Loss of stability (P = 0.0454);Loss of stability (P = 0.0454);
MVP		0.37
MPC		0.50
ClinPred		0.96	D
GERP RS		2.3
Varity_R		0.49
gMVP		0.63

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: chr12-31116863;