7-47303013-T-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_022748.12(TNS3):c.3394A>T(p.Ile1132Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00119 in 1,613,936 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (23 hom.)
• Consequence: TNS3 NM_022748.12 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.50

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009512037).
• BP6: Variant 7-47303013-T-A is Benign according to our data. Variant chr7-47303013-T-A is described in ClinVar as [Benign]. Clinvar id is 789514.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 290 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNS3	NM_022748.12	c.3394A>T	p.Ile1132Phe	missense_variant	22/31	ENST00000311160.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNS3	ENST00000311160.14	c.3394A>T	p.Ile1132Phe	missense_variant	22/31	1	NM_022748.12

Frequencies

GnomAD3 genomes AF: 0.00191 AC: 290 AN: 152202 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00282

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00207 AC: 515 AN: 249152 Hom.: 4 AF XY: 0.00187 AC XY: 253 AN XY: 135182

Gnomad AFR exome AF: 0.00252

Gnomad AMR exome AF: 0.000609

Gnomad ASJ exome AF: 0.0387

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000469

Gnomad OTH exome AF: 0.00215

GnomAD4 exome AF: 0.00111 AC: 1626 AN: 1461616 Hom.: 23 Cov.: 32 AF XY: 0.00110 AC XY: 803 AN XY: 727074

Gnomad4 AFR exome AF: 0.00305

Gnomad4 AMR exome AF: 0.000649

Gnomad4 ASJ exome AF: 0.0402

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000201

Gnomad4 OTH exome AF: 0.00363

GnomAD4 genome AF: 0.00190 AC: 290 AN: 152320 Hom.: 1 Cov.: 33 AF XY: 0.00172 AC XY: 128 AN XY: 74490

Gnomad4 AFR AF: 0.00281

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.0386

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000470

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00510 Hom.: 2

Bravo AF: 0.00215

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00254 AC: 10

ESP6500EA AF: 0.00278 AC: 23

ExAC AF: 0.00166 AC: 201

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000763

EpiControl AF: 0.000830

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.041	T
BayesDel_noAF	Pathogenic	0.28
Cadd	Uncertain	23
Dann	Uncertain	0.99
DEOGEN2	Benign	0.14	T;.
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Pathogenic	0.32	D
MetaRNN	Benign	0.0095	T;T
MetaSVM	Pathogenic	0.96	D
MutationAssessor	Uncertain	2.8	M;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.7	N;N
REVEL	Uncertain	0.55
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.024	D;.
Polyphen		1.0	D;.
Vest4		0.74
MVP		0.78
ClinPred		0.043	T
GERP RS		5.7
Varity_R		0.35
gMVP		0.44

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: rs77924433; hg19: chr7-47342611; COSMIC: COSV99053787;