5-168062044-CTTT-CTTTTTT

Variant names:

• chr5-168062044-C-CTTT
• rs11411759
• NM_001395460.1:c.1310-6_1310-4dupTTT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001395460.1(TENM2):​c.1310-6_1310-4dupTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000088 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0010 (0 hom.)
• Consequence: TENM2 NM_001395460.1 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.806
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 13 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.1310-6_1310-4dupTTT		splice_region intron	N/A	NP_001382389.1	Q9NT68-1
	TENM2	NM_001122679.2		c.1310-6_1310-4dupTTT		splice_region intron	N/A	NP_001116151.1
	TENM2	NM_001368145.1		c.854-6_854-4dupTTT		splice_region 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.1310-16_1310-15insTTT		intron	N/A	ENSP00000429430.1	Q9NT68-1
	TENM2	ENST00000520394.5	TSL:1	c.614-16_614-15insTTT		intron	N/A	ENSP00000427874.1	F8VNQ3
	TENM2	ENST00000519204.5	TSL:5	c.947-16_947-15insTTT		intron	N/A	ENSP00000428964.1	G3V106

Frequencies

GnomAD3 genomes AF: 0.0000884 AC: 13 AN: 147066 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000498

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000227

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000135

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00117 AC: 202 AN: 172048 AF XY: 0.00135

Gnomad AFR exome AF: 0.000460

Gnomad AMR exome AF: 0.000578

Gnomad ASJ exome AF: 0.00191

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00152

Gnomad NFE exome AF: 0.00129

Gnomad OTH exome AF: 0.000931

GnomAD4 exome AF: 0.00100 AC: 1335 AN: 1332214 Hom.: 0 Cov.: 0 AF XY: 0.000921 AC XY: 610 AN XY: 662262

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000267 AC: 8 AN: 29980

American (AMR) AF: 0.000474 AC: 18 AN: 37996

Ashkenazi Jewish (ASJ) AF: 0.00138 AC: 33 AN: 23962

East Asian (EAS) AF: 0.00 AC: 0 AN: 36130

South Asian (SAS) AF: 0.00161 AC: 124 AN: 77110

European-Finnish (FIN) AF: 0.000670 AC: 32 AN: 47756

Middle Eastern (MID) AF: 0.00179 AC: 7 AN: 3908

European-Non Finnish (NFE) AF: 0.00105 AC: 1074 AN: 1020192

Other (OTH) AF: 0.000707 AC: 39 AN: 55180

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000884 AC: 13 AN: 147116 Hom.: 0 Cov.: 0 AF XY: 0.0000841 AC XY: 6 AN XY: 71372

African (AFR) AF: 0.0000497 AC: 2 AN: 40208

American (AMR) AF: 0.00 AC: 0 AN: 14796

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5074

South Asian (SAS) AF: 0.00 AC: 0 AN: 4672

European-Finnish (FIN) AF: 0.000227 AC: 2 AN: 8804

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.000135 AC: 9 AN: 66882

Other (OTH) AF: 0.00 AC: 0 AN: 2032

Alfa AF: 0.00276 Hom.: 100

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.81

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11411759;

hg19: chr5-167489049;