NM_001395460.1:c.6340G>A

Variant names:

• chr5-168247279-G-A
• rs201922736
• NM_001395460.1:c.6340G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001395460.1(TENM2):​c.6340G>A​(p.Val2114Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000294 in 1,613,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00030 (0 hom.)
• Consequence: TENM2 NM_001395460.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.83
• Publications: 6 publications found

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

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08841401).
• BS2: High AC in GnomAd4 at 40 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395460.1. 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
	TENM2	NM_001395460.1	MANE Select	c.6340G>A	p.Val2114Ile	missense	Exon 29 of 31	NP_001382389.1	Q9NT68-1
	TENM2	NM_001122679.2		c.6313G>A	p.Val2105Ile	missense	Exon 28 of 30	NP_001116151.1
	TENM2	NM_001368145.1		c.5863G>A	p.Val1955Ile	missense	Exon 25 of 27	NP_001355074.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM2	ENST00000518659.6	TSL:5 MANE Select	c.6340G>A	p.Val2114Ile	missense	Exon 29 of 31	ENSP00000429430.1	Q9NT68-1
	TENM2	ENST00000520394.5	TSL:1	c.5623G>A	p.Val1875Ile	missense	Exon 23 of 25	ENSP00000427874.1	F8VNQ3
	TENM2	ENST00000519204.5	TSL:5	c.5977G>A	p.Val1993Ile	missense	Exon 26 of 28	ENSP00000428964.1	G3V106

Frequencies

GnomAD3 genomes AF: 0.000263 AC: 40 AN: 152118 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000148 AC: 37 AN: 249240 AF XY: 0.000133

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.000265

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000298 AC: 435 AN: 1461706 Hom.: 0 Cov.: 31 AF XY: 0.000294 AC XY: 214 AN XY: 727134

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000671 AC: 3 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53400

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.000363 AC: 404 AN: 1111866

Other (OTH) AF: 0.000166 AC: 10 AN: 60374

GnomAD4 genome AF: 0.000263 AC: 40 AN: 152118 Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 15 AN XY: 74282

African (AFR) AF: 0.0000966 AC: 4 AN: 41422

American (AMR) AF: 0.0000655 AC: 1 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000500 AC: 34 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000281 Hom.: 0

Bravo AF: 0.000208

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000120 AC: 1

ExAC AF: 0.0000910 AC: 11

EpiCase AF: 0.000273

EpiControl AF: 0.000771

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	0.086
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	22
DANN	Benign	0.84
DEOGEN2	Benign	0.0016	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.070
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.088	T
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Benign	0.14	N
PhyloP100		5.8
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	0.32	N
REVEL	Uncertain	0.46
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.16	B
Vest4		0.26
MVP		0.15
MPC		0.34
ClinPred		0.077	T
GERP RS		5.4
Varity_R		0.11
gMVP		0.20
Mutation Taster		=81/19	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: rs201922736; hg19: chr5-167674284; COSMIC: COSV69122175;