NM_001395460.1:c.6599A>G

Variant names:

• chr5-168247538-A-G
• NM_001395460.1:c.6599A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001395460.1(TENM2):​c.6599A>G​(p.Lys2200Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TENM2 NM_001395460.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.52

Genes affected

TENM2 (HGNC:29943): (teneurin transmembrane protein 2) Enables cell adhesion molecule binding activity and signaling receptor binding activity. Involved in several processes, including calcium-mediated signaling using intracellular calcium source; heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules; and retrograde trans-synaptic signaling by trans-synaptic protein complex. Located in cell-cell junction and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TENM2-AS1 (HGNC:56066): (TENM2 antisense RNA 2)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22602642).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM2	NM_001395460.1	c.6599A>G	p.Lys2200Arg	missense_variant	Exon 29 of 31	ENST00000518659.6	NP_001382389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM2	ENST00000518659.6	c.6599A>G	p.Lys2200Arg	missense_variant	Exon 29 of 31	5	NM_001395460.1	ENSP00000429430.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 42

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 10, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.6572A>G (p.K2191R) alteration is located in exon 27 (coding exon 27) of the TENM2 gene. This alteration results from a A to G substitution at nucleotide position 6572, causing the lysine (K) at amino acid position 2191 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0011	T;T;T
Eigen	Benign	0.050
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.85	T;T;T
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Benign	-0.56	N;.;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	0.16	N;N;N
REVEL	Uncertain	0.47
Sift	Benign	0.78	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.85	P;.;B
Vest4		0.20
MutPred		0.36		Loss of ubiquitination at K2200 (P = 0.0071);.;.;
MVP		0.28
MPC		0.68
ClinPred		0.95	D
GERP RS		5.6
Varity_R		0.15
gMVP		0.29

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-167674543;