NM_170754.4:c.77C>G

Variant names:

• chr12-53051856-C-G
• NM_170754.4:c.77C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_170754.4(TNS2):​c.77C>G​(p.Pro26Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TNS2 NM_170754.4 missense, splice_region
• Scores: Splicing: ADA: 0.9823
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.21
• Publications: 0 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. Scorers claiming Uncertain: max_spliceai. No scorers claiming Benign.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170754.4. 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.77C>G	p.Pro26Arg	missense splice_region	Exon 2 of 29	NP_736610.2
	TNS2	NM_001416204.1		c.77C>G	p.Pro26Arg	missense splice_region	Exon 2 of 29	NP_001403133.1
	TNS2	NM_001416202.1		c.77C>G	p.Pro26Arg	missense splice_region	Exon 2 of 29	NP_001403131.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNS2	ENST00000314250.11	TSL:1 MANE Select	c.77C>G	p.Pro26Arg	missense splice_region	Exon 2 of 29	ENSP00000319684.7	Q63HR2-1
	TNS2	ENST00000314276.7	TSL:1	c.107C>G	p.Pro36Arg	missense splice_region	Exon 2 of 29	ENSP00000319756.3	Q63HR2-4
	TNS2	ENST00000379902.7	TSL:1	c.-296C>G		splice_region	Exon 2 of 29	ENSP00000369232.3	Q63HR2-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	0.30
BayesDel_addAF	Uncertain	0.093	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.49	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.32	T
MetaSVM	Uncertain	0.46	D
PhyloP100		3.2
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.36
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.077	T
Polyphen		0.99	D
Vest4		0.53
MutPred		0.25		Gain of helix (P = 0.005)
MVP		0.47
MPC		0.69
ClinPred		0.95	D
GERP RS		5.4
Varity_R		0.098
gMVP		0.52
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.98
dbscSNV1_RF	Pathogenic	0.81
SpliceAI score (max)		0.30		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.30		Position offset: 4

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr12-53445640;