NM_001370302.1:c.556A>G

Variant names:

• chr12-30982631-A-G
• NM_001370302.1:c.556A>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001370302.1(TSPAN11):​c.556A>G​(p.Lys186Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TSPAN11 NM_001370302.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.00
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.778

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.556A>G	p.Lys186Glu	missense	Exon 6 of 8	NP_001357231.1	A1L157
	TSPAN11	NM_001080509.3		c.556A>G	p.Lys186Glu	missense	Exon 6 of 8	NP_001073978.1	A1L157
	TSPAN11	NM_001370301.1		c.526A>G	p.Lys176Glu	missense	Exon 5 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.556A>G	p.Lys186Glu	missense	Exon 6 of 8	ENSP00000437403.1	A1L157
	TSPAN11	ENST00000261177.10	TSL:1	c.556A>G	p.Lys186Glu	missense	Exon 6 of 8	ENSP00000261177.9	A1L157
	TSPAN11	ENST00000851526.1		c.556A>G	p.Lys186Glu	missense	Exon 6 of 8	ENSP00000521585.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460012 Hom.: 0 Cov.: 77 AF XY: 0.00 AC XY: 0 AN XY: 726286

African (AFR) AF: 0.00 AC: 0 AN: 33454

American (AMR) AF: 0.00 AC: 0 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26088

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52504

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5678

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111494

Other (OTH) AF: 0.00 AC: 0 AN: 60326

GnomAD4 genome Cov.: 35

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	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.032	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Uncertain	0.26	D
MutationAssessor	Uncertain	2.7	M
PhyloP100		9.0
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.1	D
REVEL	Pathogenic	0.68
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.014	D
Polyphen		1.0	D
Vest4		0.82
MutPred		0.57		Loss of methylation at K186 (P = 0.0015)
MVP		0.55
MPC		0.51
ClinPred		0.95	D
GERP RS		4.0
Varity_R		0.72
gMVP		0.83
Mutation Taster		=38/62	disease causing

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: chr12-31135566;