NM_001395460.1:c.577C>T

Variant names:

• chr5-167876060-C-T
• rs757858208
• NM_001395460.1:c.577C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001395460.1(TENM2):​c.577C>T​(p.Pro193Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000186 in 1,399,394 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: TENM2 NM_001395460.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.64
• 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2788372).
• BS2: High AC in GnomAdExome4 at 26 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.577C>T	p.Pro193Ser	missense	Exon 5 of 31	NP_001382389.1	Q9NT68-1
	TENM2	NM_001122679.2		c.577C>T	p.Pro193Ser	missense	Exon 4 of 30	NP_001116151.1
	TENM2	NM_001368145.1		c.121C>T	p.Pro41Ser	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.577C>T	p.Pro193Ser	missense	Exon 5 of 31	ENSP00000429430.1	Q9NT68-1
	TENM2	ENST00000520394.5	TSL:1	c.140-76528C>T		intron	N/A	ENSP00000427874.1	F8VNQ3
	TENM2	ENST00000519204.5	TSL:5	c.214C>T	p.Pro72Ser	missense	Exon 2 of 28	ENSP00000428964.1	G3V106

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.00000639 AC: 1 AN: 156586 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000405

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: 0.0000186 AC: 26 AN: 1399394 Hom.: 0 Cov.: 32 AF XY: 0.0000101 AC XY: 7 AN XY: 690210

African (AFR) AF: 0.00 AC: 0 AN: 31596

American (AMR) AF: 0.0000560 AC: 2 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.0000213 AC: 23 AN: 1078954

Other (OTH) AF: 0.0000172 AC: 1 AN: 58004

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 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	Benign	0.063
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0015	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	0.55	N
PhyloP100		4.6
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.28
Sift	Benign	0.35	T
Sift4G	Benign	0.57	T
Polyphen		1.0	D
Vest4		0.32
MutPred		0.58		Loss of glycosylation at P193 (P = 0.0514)
MVP		0.093
MPC		0.47
ClinPred		0.30	T
GERP RS		5.8
Varity_R		0.095
Mutation Taster		=42/58	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: rs757858208; hg19: chr5-167303065;