NM_001395460.1:c.226+32673T>G

Variant names:

• chr5-167317736-T-G
• rs4242220
• NM_001395460.1:c.226+32673T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001395460.1(TENM2):​c.226+32673T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 151,988 control chromosomes in the GnomAD database, including 21,082 homozygotes. 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: 𝑓 0.51 (21082 hom., cov: 32)
• Consequence: TENM2 NM_001395460.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.866
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM2	NM_001395460.1	c.226+32673T>G		intron_variant	Intron 3 of 30	ENST00000518659.6	NP_001382389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM2	ENST00000518659.6	c.226+32673T>G		intron_variant	Intron 3 of 30	5	NM_001395460.1	ENSP00000429430.1
TENM2	ENST00000695884.1	n.878+32673T>G		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77470 AN: 151868 Hom.: 21078 Cov.: 32

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.639

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.536

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.510 AC: 77483 AN: 151988 Hom.: 21082 Cov.: 32 AF XY: 0.509 AC XY: 37838 AN XY: 74268

African (AFR) AF: 0.321 AC: 13299 AN: 41464

American (AMR) AF: 0.611 AC: 9321 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 2143 AN: 3470

East Asian (EAS) AF: 0.253 AC: 1308 AN: 5160

South Asian (SAS) AF: 0.471 AC: 2263 AN: 4808

European-Finnish (FIN) AF: 0.639 AC: 6744 AN: 10558

Middle Eastern (MID) AF: 0.548 AC: 160 AN: 292

European-Non Finnish (NFE) AF: 0.598 AC: 40668 AN: 67954

Other (OTH) AF: 0.530 AC: 1120 AN: 2112

Alfa AF: 0.567 Hom.: 65225

Bravo AF: 0.504

Asia WGS AF: 0.372 AC: 1299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	12
DANN	Benign	0.56
PhyloP100		0.87
Mutation Taster		=100/0	polymorphism (auto)

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: rs4242220; hg19: chr5-166744741;