chr5-168062044-C-CTTTT

Variant names:

• chr5-168062044-C-CTTTT
• rs11411759
• NM_001395460.1:c.1310-7_1310-4dupTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001395460.1(TENM2):​c.1310-7_1310-4dupTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: TENM2 NM_001395460.1 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.806
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM2	NM_001395460.1	MANE Select	c.1310-7_1310-4dupTTTT		splice_region intron	N/A	NP_001382389.1
	TENM2	NM_001122679.2		c.1310-7_1310-4dupTTTT		splice_region intron	N/A	NP_001116151.1
	TENM2	NM_001368145.1		c.854-7_854-4dupTTTT		splice_region intron	N/A	NP_001355074.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM2	ENST00000518659.6	TSL:5 MANE Select	c.1310-16_1310-15insTTTT		intron	N/A	ENSP00000429430.1
	TENM2	ENST00000520394.5	TSL:1	c.614-16_614-15insTTTT		intron	N/A	ENSP00000427874.1
	TENM2	ENST00000519204.5	TSL:5	c.947-16_947-15insTTTT		intron	N/A	ENSP00000428964.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.0000127 AC: 17 AN: 1334260 Hom.: 0 Cov.: 0 AF XY: 0.0000136 AC XY: 9 AN XY: 663284

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

African (AFR) AF: 0.0000333 AC: 1 AN: 29990

American (AMR) AF: 0.0000789 AC: 3 AN: 38024

Ashkenazi Jewish (ASJ) AF: 0.0000417 AC: 1 AN: 24002

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

South Asian (SAS) AF: 0.0000776 AC: 6 AN: 77278

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47804

Middle Eastern (MID) AF: 0.000255 AC: 1 AN: 3914

European-Non Finnish (NFE) AF: 0.00000489 AC: 5 AN: 1021844

Other (OTH) AF: 0.00 AC: 0 AN: 55274

⚠️ 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 Cov.: 0

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

Other links and lift over

dbSNP: rs11411759; hg19: chr5-167489049;