chr5-168062044-C-CT

Variant names:

• chr5-168062044-C-CT
• rs11411759
• NM_001395460.1:c.1310-4dupT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001395460.1(TENM2):​c.1310-4dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 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 0.39 (11650 hom., cov: 0)
  • Exomes 𝑓: 0.35 (9804 hom.)
  • Failed GnomAD Quality Control
• 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.467 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM2	NM_001395460.1	MANE Select	c.1310-4dupT		splice_region intron	N/A	NP_001382389.1
	TENM2	NM_001122679.2		c.1310-4dupT		splice_region intron	N/A	NP_001116151.1
	TENM2	NM_001368145.1		c.854-4dupT		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_1310-15insT		intron	N/A	ENSP00000429430.1
	TENM2	ENST00000520394.5	TSL:1	c.614-16_614-15insT		intron	N/A	ENSP00000427874.1
	TENM2	ENST00000519204.5	TSL:5	c.947-16_947-15insT		intron	N/A	ENSP00000428964.1

Frequencies

GnomAD3 genomes AF: 0.389 AC: 57200 AN: 146910 Hom.: 11656 Cov.: 0

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.368

GnomAD2 exomes AF: 0.318 AC: 54631 AN: 172048 AF XY: 0.318

Gnomad AFR exome AF: 0.241

Gnomad AMR exome AF: 0.293

Gnomad ASJ exome AF: 0.331

Gnomad EAS exome AF: 0.195

Gnomad FIN exome AF: 0.387

Gnomad NFE exome AF: 0.356

Gnomad OTH exome AF: 0.334

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.354 AC: 463598 AN: 1310586 Hom.: 9804 Cov.: 0 AF XY: 0.351 AC XY: 228359 AN XY: 651188

African (AFR) AF: 0.243 AC: 7111 AN: 29316

American (AMR) AF: 0.260 AC: 9634 AN: 37106

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 7648 AN: 23524

East Asian (EAS) AF: 0.187 AC: 6607 AN: 35314

South Asian (SAS) AF: 0.252 AC: 19004 AN: 75394

European-Finnish (FIN) AF: 0.383 AC: 18019 AN: 47042

Middle Eastern (MID) AF: 0.301 AC: 1148 AN: 3816

European-Non Finnish (NFE) AF: 0.374 AC: 376159 AN: 1004866

Other (OTH) AF: 0.337 AC: 18268 AN: 54208

GnomAD4 genome AF: 0.389 AC: 57190 AN: 146960 Hom.: 11650 Cov.: 0 AF XY: 0.387 AC XY: 27616 AN XY: 71278

African (AFR) AF: 0.279 AC: 11199 AN: 40166

American (AMR) AF: 0.354 AC: 5222 AN: 14772

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1390 AN: 3450

East Asian (EAS) AF: 0.208 AC: 1052 AN: 5068

South Asian (SAS) AF: 0.266 AC: 1243 AN: 4670

European-Finnish (FIN) AF: 0.510 AC: 4480 AN: 8778

Middle Eastern (MID) AF: 0.313 AC: 89 AN: 284

European-Non Finnish (NFE) AF: 0.471 AC: 31476 AN: 66836

Other (OTH) AF: 0.363 AC: 736 AN: 2028

Alfa AF: 0.280 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 (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: rs11411759; hg19: chr5-167489049;