12-30979630-C-G

Variant names:

• chr12-30979630-C-G
• NM_001370302.1:c.416C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001370302.1(TSPAN11):​c.416C>G​(p.Ala139Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: TSPAN11 NM_001370302.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.59
• Publications: 0 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]

TSPAN11-AS1 (HGNC:56687): (TSPAN11 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12699783).

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.416C>G	p.Ala139Gly	missense	Exon 5 of 8	NP_001357231.1	A1L157
	TSPAN11	NM_001080509.3		c.416C>G	p.Ala139Gly	missense	Exon 5 of 8	NP_001073978.1	A1L157
	TSPAN11	NM_001370301.1		c.386C>G	p.Ala129Gly	missense	Exon 4 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.416C>G	p.Ala139Gly	missense	Exon 5 of 8	ENSP00000437403.1	A1L157
	TSPAN11	ENST00000261177.10	TSL:1	c.416C>G	p.Ala139Gly	missense	Exon 5 of 8	ENSP00000261177.9	A1L157
	TSPAN11	ENST00000851526.1		c.416C>G	p.Ala139Gly	missense	Exon 5 of 8	ENSP00000521585.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.084	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.41	N
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	1.6	L
PhyloP100		2.6
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.21
Sift	Benign	0.38	T
Sift4G	Benign	0.39	T
Polyphen		0.41	B
Vest4		0.14
MutPred		0.32		Gain of disorder (P = 0.0683)
MVP		0.56
MPC		0.18
ClinPred		0.49	T
GERP RS		3.4
Varity_R		0.038
gMVP		0.47
Mutation Taster		=87/13	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

hg19: chr12-31132565;