rs10248243

Positions:

• chr7-47472516-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_022748.12(TNS3):​c.-76+8587T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 152,280 control chromosomes in the GnomAD database, including 41 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 0.012 (41 hom., cov: 33)
• Consequence: TNS3 NM_022748.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0950

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=-0.9).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0119 (1807/152280) while in subpopulation AFR AF= 0.0413 (1715/41572). AF 95% confidence interval is 0.0396. There are 41 homozygotes in gnomad4. There are 850 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1807 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNS3	NM_022748.12	c.-76+8587T>G		intron_variant		ENST00000311160.14	NP_073585.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNS3	ENST00000311160.14	c.-76+8587T>G		intron_variant		1	NM_022748.12	ENSP00000312143

Frequencies

GnomAD3 genomes AF: 0.0118 AC: 1790 AN: 152162 Hom.: 40 Cov.: 33

Gnomad AFR AF: 0.0409

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00334

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.00958

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0119 AC: 1807 AN: 152280 Hom.: 41 Cov.: 33 AF XY: 0.0114 AC XY: 850 AN XY: 74450

Gnomad4 AFR AF: 0.0413

Gnomad4 AMR AF: 0.00333

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.00948

Alfa AF: 0.0169 Hom.: 8

Bravo AF: 0.0136

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.49

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: rs10248243; hg19: chr7-47512114;