rs115605129

Variant names:

• chr5-167284857-G-A
• rs115605129
• NM_001395460.1:c.20G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001395460.1(TENM2):​c.20G>A​(p.Arg7Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0064 in 1,551,342 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0047 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0066 (41 hom.)
• Consequence: TENM2 NM_001395460.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 9.60
• Publications: 4 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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008473635).
• BP6: Variant 5-167284857-G-A is Benign according to our data. Variant chr5-167284857-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2656025.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 709 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.20G>A	p.Arg7Gln	missense	Exon 3 of 31	NP_001382389.1	Q9NT68-1
	TENM2	NM_001122679.2		c.20G>A	p.Arg7Gln	missense	Exon 2 of 30	NP_001116151.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM2	ENST00000518659.6	TSL:5 MANE Select	c.20G>A	p.Arg7Gln	missense	Exon 3 of 31	ENSP00000429430.1	Q9NT68-1
	TENM2	ENST00000695884.1		n.672G>A		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes AF: 0.00467 AC: 710 AN: 152082 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00419

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00795

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00432 AC: 679 AN: 157014 AF XY: 0.00461

Gnomad AFR exome AF: 0.000993

Gnomad AMR exome AF: 0.00142

Gnomad ASJ exome AF: 0.00447

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00213

Gnomad NFE exome AF: 0.00768

Gnomad OTH exome AF: 0.00657

GnomAD4 exome AF: 0.00659 AC: 9218 AN: 1399142 Hom.: 41 Cov.: 31 AF XY: 0.00651 AC XY: 4494 AN XY: 690044

African (AFR) AF: 0.000855 AC: 27 AN: 31586

American (AMR) AF: 0.00143 AC: 51 AN: 35708

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 116 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00325 AC: 257 AN: 79188

European-Finnish (FIN) AF: 0.00203 AC: 100 AN: 49360

Middle Eastern (MID) AF: 0.00330 AC: 18 AN: 5450

European-Non Finnish (NFE) AF: 0.00773 AC: 8341 AN: 1078918

Other (OTH) AF: 0.00531 AC: 308 AN: 58012

GnomAD4 genome AF: 0.00466 AC: 709 AN: 152200 Hom.: 1 Cov.: 33 AF XY: 0.00466 AC XY: 347 AN XY: 74418

African (AFR) AF: 0.00123 AC: 51 AN: 41524

American (AMR) AF: 0.00419 AC: 64 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00576 AC: 20 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4818

European-Finnish (FIN) AF: 0.00160 AC: 17 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00794 AC: 540 AN: 68014

Other (OTH) AF: 0.00473 AC: 10 AN: 2112

Alfa AF: 0.00714 Hom.: 18

Bravo AF: 0.00467

TwinsUK AF: 0.00458 AC: 17

ALSPAC AF: 0.00597 AC: 23

ExAC AF: 0.00414 AC: 106

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.0028	T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D
M_CAP	Pathogenic	0.49	D
MetaRNN	Benign	0.0085	T
MetaSVM	Uncertain	0.54	D
MutationAssessor	Benign	2.0	M
PhyloP100		9.6
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.79	N
REVEL	Uncertain	0.58
Sift	Uncertain	0.011	D
Sift4G	Benign	0.070	T
Polyphen		0.99	D
Vest4		0.31
MVP		0.32
MPC		1.2
ClinPred		0.036	T
GERP RS		5.2
PromoterAI		0.015	Neutral
Varity_R		0.24
Mutation Taster		=65/35	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: rs115605129; hg19: chr5-166711862;