7-47539433-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.63

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 -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/exons	MANE	UniProt
TNS3	NM_022748.12	c.-264-10286G>C		intron_variant		ENST00000311160.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNS3	ENST00000311160.14	c.-264-10286G>C		intron_variant		1	NM_022748.12
TNS3	ENST00000442536.6	c.-265+66G>C		intron_variant, NMD_transcript_variant		1
TNS3	ENST00000434451.1	c.85-10286G>C		intron_variant		5
TNS3	ENST00000457718.6	c.46-10286G>C		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46343 AN: 152026 Hom.: 7939 Cov.: 33

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.: 0 AF XY: 0.355 AC XY: 31157 AN XY: 87810

Gnomad4 AFR exome AF: 0.137

Gnomad4 AMR exome AF: 0.377

Gnomad4 ASJ exome AF: 0.368

Gnomad4 EAS exome AF: 0.449

Gnomad4 SAS exome AF: 0.338

Gnomad4 FIN exome AF: 0.400

Gnomad4 NFE exome AF: 0.360

Gnomad4 OTH exome AF: 0.340

GnomAD4 genome AF: 0.305 AC: 46344 AN: 152144 Hom.: 7939 Cov.: 33 AF XY: 0.306 AC XY: 22735 AN XY: 74366

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.445

Gnomad4 SAS AF: 0.345

Gnomad4 FIN AF: 0.384

Gnomad4 NFE AF: 0.359

Gnomad4 OTH AF: 0.310

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
Dann	Benign	0.43

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: rs334504; hg19: chr7-47579031;