12-53052470-C-T

Variant names:

• chr12-53052470-C-T
• rs751291917
• ENST00000379902.7:c.-173C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_198316.2(TNS2):​c.-173C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000342 in 1,461,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: TNS2 NM_198316.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.51
• Publications: 1 publications found

Genes affected

TNS2 (HGNC:19737): (tensin 2) The protein encoded by this gene belongs to the tensin family. Tensin is a focal adhesion molecule that binds to actin filaments and participates in signaling pathways. This protein plays a role in regulating cell migration. Alternative splicing occurs at this locus and three transcript variants encoding three distinct isoforms have been identified. [provided by RefSeq, Jul 2008]

TNS2-AS1 (HGNC:27464): (TNS2 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.20037755).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198316.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNS2	NM_170754.4	MANE Select	c.200C>T	p.Thr67Met	missense	Exon 3 of 29	NP_736610.2
	TNS2	NM_198316.2		c.-173C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 29	NP_938072.1	Q63HR2-5
	TNS2	NM_001416204.1		c.200C>T	p.Thr67Met	missense	Exon 3 of 29	NP_001403133.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNS2	ENST00000379902.7	TSL:1	c.-173C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 29	ENSP00000369232.3	Q63HR2-5
	TNS2	ENST00000314250.11	TSL:1 MANE Select	c.200C>T	p.Thr67Met	missense	Exon 3 of 29	ENSP00000319684.7	Q63HR2-1
	TNS2	ENST00000314276.7	TSL:1	c.230C>T	p.Thr77Met	missense	Exon 3 of 29	ENSP00000319756.3	Q63HR2-4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.0000676 AC: 17 AN: 251456 AF XY: 0.000110

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000342 AC: 50 AN: 1461760 Hom.: 0 Cov.: 31 AF XY: 0.0000454 AC XY: 33 AN XY: 727190

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.000383 AC: 33 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000989 AC: 11 AN: 1111918

Other (OTH) AF: 0.0000331 AC: 2 AN: 60386

GnomAD4 genome Cov.: 30

Alfa AF: 0.0000712 Hom.: 0

ExAC AF: 0.0000659 AC: 8

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.097
FATHMM_MKL	Benign	0.22	N
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.20	T
MetaSVM	Uncertain	-0.21	T
PhyloP100		1.5
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.89	N
REVEL	Uncertain	0.37
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.052	T
Polyphen		0.99	D
Vest4		0.50
MutPred		0.46		Gain of catalytic residue at K64 (P = 9e-04)
MVP		0.28
MPC		0.75
ClinPred		0.14	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.059
gMVP		0.76
Mutation Taster		=289/11	polymorphism

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: rs751291917; hg19: chr12-53446254;