7-47280330-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_022748.12(TNS3):c.4122C>T(p.Pro1374=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00231 in 1,614,142 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0024 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (24 hom.)
• Consequence: TNS3 NM_022748.12 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.69

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 7-47280330-G-A is Benign according to our data. Variant chr7-47280330-G-A is described in ClinVar as [Benign]. Clinvar id is 728532.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.69 with no splicing effect.
• BS2: High AC in GnomAd at 361 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNS3	NM_022748.12	c.4122C>T	p.Pro1374=	synonymous_variant	29/31	ENST00000311160.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNS3	ENST00000311160.14	c.4122C>T	p.Pro1374=	synonymous_variant	29/31	1	NM_022748.12

Frequencies

GnomAD3 genomes AF: 0.00237 AC: 361 AN: 152174 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00157

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00870

Gnomad FIN AF: 0.00217

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.00210

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00298 AC: 743 AN: 249538 Hom.: 4 AF XY: 0.00353 AC XY: 478 AN XY: 135384

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.00113

Gnomad ASJ exome AF: 0.00189

Gnomad EAS exome AF: 0.0000556

Gnomad SAS exome AF: 0.0106

Gnomad FIN exome AF: 0.00241

Gnomad NFE exome AF: 0.00238

Gnomad OTH exome AF: 0.00346

GnomAD4 exome AF: 0.00230 AC: 3369 AN: 1461850 Hom.: 24 Cov.: 34 AF XY: 0.00263 AC XY: 1910 AN XY: 727228

Gnomad4 AFR exome AF: 0.00137

Gnomad4 AMR exome AF: 0.00136

Gnomad4 ASJ exome AF: 0.00149

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.0111

Gnomad4 FIN exome AF: 0.00240

Gnomad4 NFE exome AF: 0.00170

Gnomad4 OTH exome AF: 0.00277

GnomAD4 genome AF: 0.00236 AC: 360 AN: 152292 Hom.: 1 Cov.: 32 AF XY: 0.00247 AC XY: 184 AN XY: 74470

Gnomad4 AFR AF: 0.00156

Gnomad4 AMR AF: 0.00131

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00871

Gnomad4 FIN AF: 0.00217

Gnomad4 NFE AF: 0.00210

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00247 Hom.: 1

Bravo AF: 0.00226

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.00382

EpiControl AF: 0.00350

ClinVar

Significance: 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	CeGaT Center for Human Genetics Tuebingen	May 01, 2023	TNS3: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
Cadd	Benign	1.8
Dann	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs183336114; hg19: chr7-47319928; COSMIC: COSV60794637; COSMIC: COSV60794637;