rs74464871

Variant names:

• chr5-168246948-C-A
• NM_001395460.1:c.6009C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-168246948-C-A
• chr5-168246948-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001395460.1(TENM2):​c.6009C>A​(p.Asp2003Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TENM2 NM_001395460.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.814

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18287432).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM2	NM_001395460.1	c.6009C>A	p.Asp2003Glu	missense_variant	Exon 29 of 31	ENST00000518659.6	NP_001382389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM2	ENST00000518659.6	c.6009C>A	p.Asp2003Glu	missense_variant	Exon 29 of 31	5	NM_001395460.1	ENSP00000429430.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461700 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727130

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	0.32
DANN	Uncertain	0.99
DEOGEN2	Benign	0.065	T;T;T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.32	N
LIST_S2	Uncertain	0.86	D;D;D
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Uncertain	0.054	D
MutationAssessor	Benign	1.2	L;.;.
PrimateAI	Uncertain	0.79	T
PROVEAN	Uncertain	-2.5	D;N;N
REVEL	Pathogenic	0.66
Sift	Benign	0.29	T;T;T
Sift4G	Benign	0.36	T;T;T
Polyphen		0.42	B;.;D
Vest4		0.35
MutPred		0.43		Loss of sheet (P = 0.0457);.;.;
MVP		0.57
MPC		0.47
ClinPred		0.73	D
GERP RS		-2.7
Varity_R		0.39
gMVP		0.27

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-167673953;