7-47303115-G-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_022748.12(TNS3):c.3292C>G(p.Leu1098Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00651 in 1,614,048 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0052 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0066 (63 hom.)
• Consequence: TNS3 NM_022748.12 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 8.85

Genes affected

TNS3 (HGNC:21616): (tensin 3) Predicted to enable phosphatase activity. Predicted to be involved in dephosphorylation and intracellular signal transduction. Predicted to act upstream of or within cell migration; lung alveolus development; and positive regulation of cell population proliferation. Located in cytosol and focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008170128).
• BP6: Variant 7-47303115-G-C is Benign according to our data. Variant chr7-47303115-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 713684.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 797 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNS3	NM_022748.12	c.3292C>G	p.Leu1098Val	missense_variant	22/31	ENST00000311160.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNS3	ENST00000311160.14	c.3292C>G	p.Leu1098Val	missense_variant	22/31	1	NM_022748.12

Frequencies

GnomAD3 genomes AF: 0.00523 AC: 797 AN: 152246 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00108

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00281

Gnomad ASJ AF: 0.00547

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0187

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00700

Gnomad OTH AF: 0.00574

GnomAD3 exomes AF: 0.00557 AC: 1382 AN: 248274 Hom.: 14 AF XY: 0.00576 AC XY: 777 AN XY: 134984

Gnomad AFR exome AF: 0.00118

Gnomad AMR exome AF: 0.00241

Gnomad ASJ exome AF: 0.00748

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000752

Gnomad FIN exome AF: 0.0153

Gnomad NFE exome AF: 0.00717

Gnomad OTH exome AF: 0.00779

GnomAD4 exome AF: 0.00664 AC: 9710 AN: 1461686 Hom.: 63 Cov.: 32 AF XY: 0.00653 AC XY: 4751 AN XY: 727122

Gnomad4 AFR exome AF: 0.000956

Gnomad4 AMR exome AF: 0.00253

Gnomad4 ASJ exome AF: 0.00685

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000730

Gnomad4 FIN exome AF: 0.0144

Gnomad4 NFE exome AF: 0.00739

Gnomad4 OTH exome AF: 0.00533

GnomAD4 genome AF: 0.00523 AC: 797 AN: 152362 Hom.: 3 Cov.: 33 AF XY: 0.00548 AC XY: 408 AN XY: 74504

Gnomad4 AFR AF: 0.00108

Gnomad4 AMR AF: 0.00281

Gnomad4 ASJ AF: 0.00547

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0187

Gnomad4 NFE AF: 0.00700

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00672 Hom.: 3

Bravo AF: 0.00417

TwinsUK AF: 0.00782 AC: 29

ALSPAC AF: 0.00519 AC: 20

ESP6500AA AF: 0.00102 AC: 4

ESP6500EA AF: 0.00616 AC: 51

ExAC AF: 0.00540 AC: 653

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00747

EpiControl AF: 0.0101

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2023	TNS3: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Pathogenic	0.17
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.64	D;.
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D
MetaRNN	Benign	0.0082	T;T
MetaSVM	Pathogenic	0.92	D
MutationAssessor	Pathogenic	3.3	M;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Uncertain	0.48
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0050	D;.
Polyphen		1.0	D;.
Vest4		0.58
MVP		0.92
ClinPred		0.035	T
GERP RS		5.5
Varity_R		0.33
gMVP		0.33

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

LitVar

Other links and lift over

dbSNP: rs188962919; hg19: chr7-47342713;