5-167876040-C-G

Variant names:

• chr5-167876040-C-G
• rs376220839
• NM_001395460.1:c.557C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001395460.1(TENM2):​c.557C>G​(p.Pro186Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P186L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: TENM2 NM_001395460.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.30
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39588326).

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.557C>G	p.Pro186Arg	missense	Exon 5 of 31	NP_001382389.1	Q9NT68-1
	TENM2	NM_001122679.2		c.557C>G	p.Pro186Arg	missense	Exon 4 of 30	NP_001116151.1
	TENM2	NM_001368145.1		c.101C>G	p.Pro34Arg	missense	Exon 2 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.557C>G	p.Pro186Arg	missense	Exon 5 of 31	ENSP00000429430.1	Q9NT68-1
	TENM2	ENST00000520394.5	TSL:1	c.140-76548C>G		intron	N/A	ENSP00000427874.1	F8VNQ3
	TENM2	ENST00000519204.5	TSL:5	c.194C>G	p.Pro65Arg	missense	Exon 2 of 28	ENSP00000428964.1	G3V106

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.072	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0021	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.1	L
PhyloP100		6.3
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.24
Sift	Benign	0.052	T
Sift4G	Uncertain	0.0020	D
Polyphen		0.96	D
Vest4		0.54
MutPred		0.43		Loss of glycosylation at P186 (P = 0.0323)
MVP		0.082
MPC		0.56
ClinPred		0.87	D
GERP RS		5.0
Varity_R		0.16
Mutation Taster		=59/41	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: rs376220839; hg19: chr5-167303045;