Genetic Variant TNS3:c.-264-10286G>C (chr7-47539433-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022748.12(TNS3):c.-264-10286G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 315,550 control chromosomes in the GnomAD database, including 18,232 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.30 ( 7939 hom., cov: 33)

Exomes 𝑓: 0.36 ( 10293 hom. )

Consequence

TNS3
NM_022748.12 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.63

Publications

3 publications found

Variant links:

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]

TNS3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNS3	NM_022748.12 link	c.-264-10286G>C		intron_variant	Intron 1 of 30	ENST00000311160.14	NP_073585.8	Q68CZ2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNS3	ENST00000311160.14 link	c.-264-10286G>C		intron_variant	Intron 1 of 30	1	NM_022748.12	ENSP00000312143.9		Q68CZ2-1

Frequencies

GnomAD3 genomes

AF:

0.305

AC:

46343

AN:

152026

Hom.:

7939

Cov.:

show subpopulations

Gnomad AFR

AF:

0.145

Gnomad AMI

AF:

0.440

Gnomad AMR

AF:

0.359

Gnomad ASJ

AF:

0.371

Gnomad EAS

AF:

0.445

Gnomad SAS

AF:

0.345

Gnomad FIN

AF:

0.384

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.359

Gnomad OTH

AF:

0.311

GnomAD4 exome

AF:

0.355

AC:

58014

AN:

163406

Hom.:

10293

Cov.:

AF XY:

0.355

AC XY:

31157

AN XY:

87810

show subpopulations

African (AFR)

AF:

0.137

AC:

652

AN:

4748

American (AMR)

AF:

0.377

AC:

3205

AN:

8496

Ashkenazi Jewish (ASJ)

AF:

0.368

AC:

1411

AN:

3830

East Asian (EAS)

AF:

0.449

AC:

3246

AN:

7236

South Asian (SAS)

AF:

0.338

AC:

10190

AN:

30146

European-Finnish (FIN)

AF:

0.400

AC:

2975

AN:

7430

Middle Eastern (MID)

AF:

0.286

AC:

164

AN:

574

European-Non Finnish (NFE)

AF:

0.360

AC:

33407

AN:

92818

Other (OTH)

AF:

0.340

AC:

2764

AN:

8128

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

1708

3416

5123

6831

8539

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

252

504

756

1008

1260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.305

AC:

46344

AN:

152144

Hom.:

7939

Cov.:

AF XY:

0.306

AC XY:

22735

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.145

AC:

6005

AN:

41528

American (AMR)

AF:

0.359

AC:

5479

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.371

AC:

1289

AN:

3472

East Asian (EAS)

AF:

0.445

AC:

2299

AN:

5166

South Asian (SAS)

AF:

0.345

AC:

1665

AN:

4826

European-Finnish (FIN)

AF:

0.384

AC:

4062

AN:

10566

Middle Eastern (MID)

AF:

0.279

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.359

AC:

24409

AN:

67988

Other (OTH)

AF:

0.310

AC:

654

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1626

3252

4878

6504

8130

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

478

956

1434

1912

2390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.195

Hom.:

459

Bravo

AF:

0.300

Asia WGS

AF:

0.354

AC:

1228

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.64

(source)

DANN

Benign

0.43

PhyloP100

-2.6

PromoterAI

0.019

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over