12-30982593-G-A

Variant names:

• chr12-30982593-G-A
• rs751983677
• NM_001370302.1:c.518G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001370302.1(TSPAN11):​c.518G>A​(p.Arg173Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,613,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 35)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: TSPAN11 NM_001370302.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.89

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]

ENSG00000290531 (HGNC:56687): (TSPAN11 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 12-30982593-G-A is Benign according to our data. Variant chr12-30982593-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2468589.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPAN11	NM_001370302.1	c.518G>A	p.Arg173Gln	missense_variant	Exon 6 of 8	ENST00000546076.6	NP_001357231.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPAN11	ENST00000546076.6	c.518G>A	p.Arg173Gln	missense_variant	Exon 6 of 8	2	NM_001370302.1	ENSP00000437403.1
TSPAN11	ENST00000261177.10	c.518G>A	p.Arg173Gln	missense_variant	Exon 6 of 8	1		ENSP00000261177.9
TSPAN11	ENST00000535215.5	c.305G>A	p.Arg102Gln	missense_variant	Exon 5 of 7	2		ENSP00000445503.1
ENSG00000290531	ENST00000613860.4	n.508-3918C>T		intron_variant	Intron 5 of 5	5

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152238 Hom.: 0 Cov.: 35

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000401 AC: 10 AN: 249542 Hom.: 0 AF XY: 0.0000222 AC XY: 3 AN XY: 135396

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000178

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000294 AC: 43 AN: 1460656 Hom.: 0 Cov.: 77 AF XY: 0.0000261 AC XY: 19 AN XY: 726612

Gnomad4 AFR exome AF: 0.000269

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000189

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152356 Hom.: 0 Cov.: 35 AF XY: 0.0000671 AC XY: 5 AN XY: 74498

Gnomad4 AFR AF: 0.0000962

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000264

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 14, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.23
DANN	Benign	0.81
DEOGEN2	Benign	0.073	T;.;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.22	.;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.025	T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.84	L;.;L
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.19	N;N;N
REVEL	Benign	0.15
Sift	Benign	0.63	T;T;T
Sift4G	Benign	0.60	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.064
MutPred		0.40		Loss of helix (P = 0.2662);.;Loss of helix (P = 0.2662);
MVP		0.067
MPC		0.086
ClinPred		0.016	T
GERP RS		-8.0
Varity_R		0.023
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.43		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.43		Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs751983677; hg19: chr12-31135528;