12-53051905-A-C

Variant names:

• chr12-53051905-A-C
• NM_170754.4:c.126A>C
• TNS2 p.Lys42Asn

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_170754.4(TNS2):​c.126A>C​(p.Lys42Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TNS2 NM_170754.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.158
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.126A>C	p.Lys42Asn	missense	Exon 2 of 29	NP_736610.2
	TNS2	NM_001416204.1		c.126A>C	p.Lys42Asn	missense	Exon 2 of 29	NP_001403133.1
	TNS2	NM_001416202.1		c.126A>C	p.Lys42Asn	missense	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.126A>C	p.Lys42Asn	missense	Exon 2 of 29	ENSP00000319684.7	Q63HR2-1
	TNS2	ENST00000314276.7	TSL:1	c.156A>C	p.Lys52Asn	missense	Exon 2 of 29	ENSP00000319756.3	Q63HR2-4
	TNS2	ENST00000379902.7	TSL:1	c.-247A>C		5_prime_UTR	Exon 2 of 29	ENSP00000369232.3	Q63HR2-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Benign	0.000024
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.82	T
M_CAP	Pathogenic	0.38	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Uncertain	0.58	D
PhyloP100		0.16
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.41
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.034	D
Varity_R		0.21
gMVP		0.61
Mutation Taster		=96/4	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-53445689;