12-30963941-C-A

Variant names:

• chr12-30963941-C-A
• rs145078714
• NM_001370302.1:c.200C>A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001370302.1(TSPAN11):​c.200C>A​(p.Ala67Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A67V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TSPAN11 NM_001370302.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.63
• Publications: 2 publications found

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

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.964

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370302.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN11	NM_001370302.1	MANE Select	c.200C>A	p.Ala67Glu	missense	Exon 3 of 8	NP_001357231.1	A1L157
	TSPAN11	NM_001080509.3		c.200C>A	p.Ala67Glu	missense	Exon 3 of 8	NP_001073978.1	A1L157
	TSPAN11	NM_001370301.1		c.170C>A	p.Ala57Glu	missense	Exon 2 of 7	NP_001357230.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN11	ENST00000546076.6	TSL:2 MANE Select	c.200C>A	p.Ala67Glu	missense	Exon 3 of 8	ENSP00000437403.1	A1L157
	TSPAN11	ENST00000261177.10	TSL:1	c.200C>A	p.Ala67Glu	missense	Exon 3 of 8	ENSP00000261177.9	A1L157
	TSPAN11	ENST00000851526.1		c.200C>A	p.Ala67Glu	missense	Exon 3 of 8	ENSP00000521585.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.59	D
Eigen	Uncertain	0.38
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.044	D
MetaRNN	Pathogenic	0.96	D
MetaSVM	Uncertain	0.36	D
MutationAssessor	Pathogenic	3.6	H
PhyloP100		4.6
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-4.1	D
REVEL	Pathogenic	0.72
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.99	D
Vest4		0.84
MutPred		0.81		Gain of sheet (P = 0.1451)
MVP		0.59
MPC		0.45
ClinPred		1.0	D
GERP RS		2.6
Varity_R		0.96
gMVP		0.87
Mutation Taster		=64/36	polymorphism

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

Other links and lift over

dbSNP: rs145078714; hg19: chr12-31116876;