chr5-167799974-G-A

Variant names:

• chr5-167799974-G-A
• rs1549309
• NM_001395460.1:c.503-76012G>A

Variant summary

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

The NM_001395460.1(TENM2):​c.503-76012G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,098 control chromosomes in the GnomAD database, including 2,700 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 0.18 (2700 hom., cov: 33)
• Consequence: TENM2 NM_001395460.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.564
• Publications: 9 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.205 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.503-76012G>A		intron	N/A	NP_001382389.1	Q9NT68-1
	TENM2	NM_001122679.2		c.503-76012G>A		intron	N/A	NP_001116151.1
	TENM2	NM_001368145.1		c.47-76012G>A		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.503-76012G>A		intron	N/A	ENSP00000429430.1	Q9NT68-1
	TENM2	ENST00000520394.5	TSL:1	c.139+44782G>A		intron	N/A	ENSP00000427874.1	F8VNQ3
	TENM2	ENST00000519204.5	TSL:5	c.139+44782G>A		intron	N/A	ENSP00000428964.1	G3V106

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27768 AN: 151980 Hom.: 2695 Cov.: 33

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.183 AC: 27791 AN: 152098 Hom.: 2700 Cov.: 33 AF XY: 0.185 AC XY: 13787 AN XY: 74342

African (AFR) AF: 0.209 AC: 8673 AN: 41498

American (AMR) AF: 0.162 AC: 2469 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 759 AN: 3472

East Asian (EAS) AF: 0.119 AC: 616 AN: 5158

South Asian (SAS) AF: 0.164 AC: 790 AN: 4812

European-Finnish (FIN) AF: 0.246 AC: 2596 AN: 10574

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11380 AN: 67990

Other (OTH) AF: 0.175 AC: 371 AN: 2114

Alfa AF: 0.172 Hom.: 2879

Bravo AF: 0.176

Asia WGS AF: 0.157 AC: 549 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.30
DANN	Benign	0.36
PhyloP100		-0.56
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: rs1549309; hg19: chr5-167226979; COSMIC: COSV72854093;