chr5-168062044-CTT-C

Variant names:

• chr5-168062044-CTT-C
• rs11411759
• NM_001395460.1:c.1310-5_1310-4delTT

Variant summary

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

The NM_001395460.1(TENM2):​c.1310-5_1310-4delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 1,464,538 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000082 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0024 (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: 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.1310-5_1310-4delTT		splice_region intron	N/A	NP_001382389.1
	TENM2	NM_001122679.2		c.1310-5_1310-4delTT		splice_region intron	N/A	NP_001116151.1
	TENM2	NM_001368145.1		c.854-5_854-4delTT		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.1310-15_1310-14delTT		intron	N/A	ENSP00000429430.1
	TENM2	ENST00000520394.5	TSL:1	c.614-15_614-14delTT		intron	N/A	ENSP00000427874.1
	TENM2	ENST00000519204.5	TSL:5	c.947-15_947-14delTT		intron	N/A	ENSP00000428964.1

Frequencies

GnomAD3 genomes AF: 0.0000680 AC: 10 AN: 147050 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000748

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000197

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000227

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000449

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0102 AC: 1758 AN: 172048 AF XY: 0.0104

Gnomad AFR exome AF: 0.0127

Gnomad AMR exome AF: 0.00445

Gnomad ASJ exome AF: 0.00574

Gnomad EAS exome AF: 0.0277

Gnomad FIN exome AF: 0.00750

Gnomad NFE exome AF: 0.00772

Gnomad OTH exome AF: 0.00838

GnomAD4 exome AF: 0.00237 AC: 3128 AN: 1317438 Hom.: 0 AF XY: 0.00267 AC XY: 1748 AN XY: 654368

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

African (AFR) AF: 0.00454 AC: 133 AN: 29270

American (AMR) AF: 0.00357 AC: 134 AN: 37512

Ashkenazi Jewish (ASJ) AF: 0.00326 AC: 77 AN: 23634

East Asian (EAS) AF: 0.00977 AC: 334 AN: 34182

South Asian (SAS) AF: 0.00832 AC: 623 AN: 74880

European-Finnish (FIN) AF: 0.00427 AC: 201 AN: 47036

Middle Eastern (MID) AF: 0.00311 AC: 12 AN: 3856

European-Non Finnish (NFE) AF: 0.00148 AC: 1494 AN: 1012566

Other (OTH) AF: 0.00220 AC: 120 AN: 54502

⚠️ 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: 0.0000816 AC: 12 AN: 147100 Hom.: 0 Cov.: 0 AF XY: 0.0000701 AC XY: 5 AN XY: 71358

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

African (AFR) AF: 0.0000746 AC: 3 AN: 40206

American (AMR) AF: 0.00 AC: 0 AN: 14794

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.000197 AC: 1 AN: 5074

South Asian (SAS) AF: 0.000214 AC: 1 AN: 4672

European-Finnish (FIN) AF: 0.000227 AC: 2 AN: 8802

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

European-Non Finnish (NFE) AF: 0.0000449 AC: 3 AN: 66874

Other (OTH) AF: 0.000492 AC: 1 AN: 2032

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00529677), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0157 Hom.: 100

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.81
Mutation Taster		=100/0	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: rs11411759; hg19: chr5-167489049;