7-47291996-G-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.3887C>T(p.Thr1296Met) variant causes a missense change. The variant allele was found at a frequency of 0.00753 in 1,614,146 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0051 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0078 (59 hom.)
• Consequence: TNS3 NM_022748.12 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.97

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=0.008240819).
• BP6: Variant 7-47291996-G-A is Benign according to our data. Variant chr7-47291996-G-A is described in ClinVar as [Benign]. Clinvar id is 770935.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 776 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNS3	NM_022748.12	c.3887C>T	p.Thr1296Met	missense_variant	27/31	ENST00000311160.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNS3	ENST00000311160.14	c.3887C>T	p.Thr1296Met	missense_variant	27/31	1	NM_022748.12

Frequencies

GnomAD3 genomes AF: 0.00510 AC: 776 AN: 152196 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00399

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00734

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00830

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00500 AC: 1246 AN: 249358 Hom.: 6 AF XY: 0.00498 AC XY: 674 AN XY: 135280

Gnomad AFR exome AF: 0.00116

Gnomad AMR exome AF: 0.00252

Gnomad ASJ exome AF: 0.00318

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00830

Gnomad NFE exome AF: 0.00787

Gnomad OTH exome AF: 0.00661

GnomAD4 exome AF: 0.00778 AC: 11376 AN: 1461832 Hom.: 59 Cov.: 30 AF XY: 0.00760 AC XY: 5529 AN XY: 727220

Gnomad4 AFR exome AF: 0.00119

Gnomad4 AMR exome AF: 0.00264

Gnomad4 ASJ exome AF: 0.00230

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.00884

Gnomad4 NFE exome AF: 0.00929

Gnomad4 OTH exome AF: 0.00573

GnomAD4 genome AF: 0.00509 AC: 776 AN: 152314 Hom.: 2 Cov.: 33 AF XY: 0.00470 AC XY: 350 AN XY: 74476

Gnomad4 AFR AF: 0.00142

Gnomad4 AMR AF: 0.00399

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00734

Gnomad4 NFE AF: 0.00830

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00688 Hom.: 6

Bravo AF: 0.00470

TwinsUK AF: 0.0111 AC: 41

ALSPAC AF: 0.0101 AC: 39

ESP6500AA AF: 0.00161 AC: 6

ESP6500EA AF: 0.00840 AC: 69

ExAC AF: 0.00459 AC: 555

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00627

EpiControl AF: 0.00694

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

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Uncertain	-0.010
Cadd	Uncertain	26
Dann	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.0082	T
MetaSVM	Uncertain	0.78	D
MutationAssessor	Uncertain	2.7	M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.0070	D
Polyphen		1.0	D
Vest4		0.29
MVP		0.82
ClinPred		0.027	T
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.084
gMVP		0.39

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: rs41280696; hg19: chr7-47331594;