rs745482697

Variant names:

• chr5-168244457-G-A
• rs745482697
• NM_001395460.1:c.5558G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-168244457-G-A
• chr5-168244457-G-T

Variant summary

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

The NM_001395460.1(TENM2):​c.5558G>A​(p.Arg1853Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000444 in 1,578,272 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: TENM2 NM_001395460.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.15
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.5558G>A	p.Arg1853Gln	missense	Exon 28 of 31	NP_001382389.1	Q9NT68-1
	TENM2	NM_001122679.2		c.5531G>A	p.Arg1844Gln	missense	Exon 27 of 30	NP_001116151.1
	TENM2	NM_001368145.1		c.5081G>A	p.Arg1694Gln	missense	Exon 24 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.5558G>A	p.Arg1853Gln	missense	Exon 28 of 31	ENSP00000429430.1	Q9NT68-1
	TENM2	ENST00000520394.5	TSL:1	c.4841G>A	p.Arg1614Gln	missense	Exon 22 of 25	ENSP00000427874.1	F8VNQ3
	TENM2	ENST00000519204.5	TSL:5	c.5195G>A	p.Arg1732Gln	missense	Exon 25 of 28	ENSP00000428964.1	G3V106

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152176 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00000424 AC: 1 AN: 235658 AF XY: 0.00

Gnomad AFR exome AF: 0.0000667

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000280 AC: 4 AN: 1426096 Hom.: 0 Cov.: 31 AF XY: 0.00000284 AC XY: 2 AN XY: 704682

African (AFR) AF: 0.00 AC: 0 AN: 32588

American (AMR) AF: 0.00 AC: 0 AN: 41934

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25238

East Asian (EAS) AF: 0.00 AC: 0 AN: 38504

South Asian (SAS) AF: 0.00 AC: 0 AN: 82490

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52916

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5636

European-Non Finnish (NFE) AF: 0.00000276 AC: 3 AN: 1088162

Other (OTH) AF: 0.0000171 AC: 1 AN: 58628

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152176 Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2 AN XY: 74338

African (AFR) AF: 0.0000483 AC: 2 AN: 41434

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.00000828 AC: 1

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	Uncertain	0.35
BayesDel_addAF	Uncertain	0.045	T
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.091	T
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Pathogenic	0.34	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Uncertain	0.52	D
MutationAssessor	Benign	1.6	L
PhyloP100		8.1
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.59
Sift	Benign	0.17	T
Sift4G	Benign	0.11	T
Polyphen		1.0	D
Vest4		0.80
MutPred		0.38		Loss of MoRF binding (P = 0.0565)
MVP		0.13
MPC		1.3
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.51
gMVP		0.60
Mutation Taster		=40/60	disease causing

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: rs745482697; hg19: chr5-167671462; COSMIC: COSV69124084; COSMIC: COSV69124084;