5-168247068-C-T

Variant names:

• chr5-168247068-C-T
• rs116810963
• NM_001395460.1:c.6129C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_001395460.1(TENM2):​c.6129C>T​(p.Asp2043Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000811 in 1,613,918 control chromosomes in the GnomAD database, including 8 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 0.0040 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00048 (4 hom.)
• Consequence: TENM2 NM_001395460.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.168
• 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]

TENM2-AS1 (HGNC:56066): (TENM2 antisense RNA 2)

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=0.168 with no splicing effect.
• BS2: High AC in GnomAd4 at 612 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.6129C>T	p.Asp2043Asp	synonymous	Exon 29 of 31	NP_001382389.1	Q9NT68-1
	TENM2	NM_001122679.2		c.6102C>T	p.Asp2034Asp	synonymous	Exon 28 of 30	NP_001116151.1
	TENM2	NM_001368145.1		c.5652C>T	p.Asp1884Asp	synonymous	Exon 25 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.6129C>T	p.Asp2043Asp	synonymous	Exon 29 of 31	ENSP00000429430.1	Q9NT68-1
	TENM2	ENST00000520394.5	TSL:1	c.5412C>T	p.Asp1804Asp	synonymous	Exon 23 of 25	ENSP00000427874.1	F8VNQ3
	TENM2	ENST00000519204.5	TSL:5	c.5766C>T	p.Asp1922Asp	synonymous	Exon 26 of 28	ENSP00000428964.1	G3V106

Frequencies

GnomAD3 genomes AF: 0.00400 AC: 608 AN: 152102 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00121 AC: 301 AN: 249158 AF XY: 0.000925

Gnomad AFR exome AF: 0.0161

Gnomad AMR exome AF: 0.00113

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000531

Gnomad OTH exome AF: 0.000661

GnomAD4 exome AF: 0.000477 AC: 697 AN: 1461698 Hom.: 4 Cov.: 31 AF XY: 0.000389 AC XY: 283 AN XY: 727130

African (AFR) AF: 0.0156 AC: 523 AN: 33480

American (AMR) AF: 0.00130 AC: 58 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.0000459 AC: 51 AN: 1111860

Other (OTH) AF: 0.000911 AC: 55 AN: 60374

GnomAD4 genome AF: 0.00402 AC: 612 AN: 152220 Hom.: 4 Cov.: 32 AF XY: 0.00390 AC XY: 290 AN XY: 74418

African (AFR) AF: 0.0139 AC: 577 AN: 41546

American (AMR) AF: 0.00144 AC: 22 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68020

Other (OTH) AF: 0.00378 AC: 8 AN: 2114

Alfa AF: 0.00147 Hom.: 0

Bravo AF: 0.00483

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	5.1
DANN	Benign	0.89
PhyloP100		0.17
Mutation Taster		=81/19	polymorphism

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: rs116810963; hg19: chr5-167674073; COSMIC: COSV69128941;