7-47539433-C-G

Variant names:

• chr7-47539433-C-G
• rs334504
• NM_022748.12:c.-264-10286G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

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	c.-264-10286G>C		intron_variant	Intron 1 of 30	ENST00000311160.14	NP_073585.8

Ensembl

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

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

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

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

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: 82 AN: 294

European-Non Finnish (NFE) AF: 0.359 AC: 24409 AN: 67988

Other (OTH) AF: 0.310 AC: 654 AN: 2112

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
PhyloP100		-2.6
PromoterAI		0.019	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs334504; hg19: chr7-47579031;