chr5-167883422-T-C

Variant names:

• chr5-167883422-T-C
• rs1421985
• NM_001395460.1:c.712+7227T>C

Variant summary

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

The NM_001395460.1(TENM2):​c.712+7227T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 152,178 control chromosomes in the GnomAD database, including 17,876 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 0.45 (17876 hom., cov: 33)
• Consequence: TENM2 NM_001395460.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.498
• Publications: 2 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

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.712+7227T>C		intron	N/A	NP_001382389.1	Q9NT68-1
	TENM2	NM_001122679.2		c.712+7227T>C		intron	N/A	NP_001116151.1
	TENM2	NM_001368145.1		c.256+7227T>C		intron	N/A	NP_001355074.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM2	ENST00000518659.6	TSL:5 MANE Select	c.712+7227T>C		intron	N/A	ENSP00000429430.1	Q9NT68-1
	TENM2	ENST00000520394.5	TSL:1	c.140-69166T>C		intron	N/A	ENSP00000427874.1	F8VNQ3
	TENM2	ENST00000519204.5	TSL:5	c.349+7227T>C		intron	N/A	ENSP00000428964.1	G3V106

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68713 AN: 152060 Hom.: 17878 Cov.: 33

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.477

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

GnomAD4 genome AF: 0.452 AC: 68723 AN: 152178 Hom.: 17876 Cov.: 33 AF XY: 0.454 AC XY: 33750 AN XY: 74388

African (AFR) AF: 0.198 AC: 8233 AN: 41534

American (AMR) AF: 0.480 AC: 7346 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.628 AC: 2180 AN: 3472

East Asian (EAS) AF: 0.242 AC: 1251 AN: 5166

South Asian (SAS) AF: 0.573 AC: 2764 AN: 4824

European-Finnish (FIN) AF: 0.589 AC: 6232 AN: 10584

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.577 AC: 39243 AN: 67992

Other (OTH) AF: 0.474 AC: 1001 AN: 2114

Alfa AF: 0.523 Hom.: 53705

Bravo AF: 0.426

Asia WGS AF: 0.377 AC: 1313 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	12
DANN	Benign	0.44
PhyloP100		0.50
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: rs1421985; hg19: chr5-167310427;