5-168062044-CTTT-CTTTTT

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001395460.1(TENM2):​c.1310-5_1310-4dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.085 (662 hom., cov: 0)
  • Exomes 𝑓: 0.11 (434 hom.)
• Consequence: TENM2 NM_001395460.1 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 5-168062044-C-CTT is Benign according to our data. Variant chr5-168062044-C-CTT is described in ClinVar as Benign. ClinVar VariationId is 403528.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.151 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM2	NM_001395460.1	MANE Select	c.1310-5_1310-4dupTT		splice_region intron	N/A	NP_001382389.1	Q9NT68-1
	TENM2	NM_001122679.2		c.1310-5_1310-4dupTT		splice_region intron	N/A	NP_001116151.1
	TENM2	NM_001368145.1		c.854-5_854-4dupTT		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_1310-15insTT		intron	N/A	ENSP00000429430.1	Q9NT68-1
	TENM2	ENST00000520394.5	TSL:1	c.614-16_614-15insTT		intron	N/A	ENSP00000427874.1	F8VNQ3
	TENM2	ENST00000519204.5	TSL:5	c.947-16_947-15insTT		intron	N/A	ENSP00000428964.1	G3V106

Frequencies

GnomAD3 genomes AF: 0.0855 AC: 12563 AN: 147002 Hom.: 664 Cov.: 0

Gnomad AFR AF: 0.0364

Gnomad AMI AF: 0.0815

Gnomad AMR AF: 0.0930

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.00256

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.0964

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.116

GnomAD2 exomes AF: 0.0853 AC: 14671 AN: 172048 AF XY: 0.0895

Gnomad AFR exome AF: 0.0315

Gnomad AMR exome AF: 0.0545

Gnomad ASJ exome AF: 0.137

Gnomad EAS exome AF: 0.00232

Gnomad FIN exome AF: 0.0854

Gnomad NFE exome AF: 0.0972

Gnomad OTH exome AF: 0.0996

GnomAD4 exome AF: 0.108 AC: 140929 AN: 1302388 Hom.: 434 Cov.: 0 AF XY: 0.109 AC XY: 70613 AN XY: 647566

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

African (AFR) AF: 0.0329 AC: 978 AN: 29682

American (AMR) AF: 0.0523 AC: 1966 AN: 37618

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 3207 AN: 23504

East Asian (EAS) AF: 0.00164 AC: 59 AN: 36054

South Asian (SAS) AF: 0.134 AC: 10164 AN: 75582

European-Finnish (FIN) AF: 0.0894 AC: 4190 AN: 46850

Middle Eastern (MID) AF: 0.140 AC: 543 AN: 3866

European-Non Finnish (NFE) AF: 0.115 AC: 114159 AN: 995160

Other (OTH) AF: 0.105 AC: 5663 AN: 54072

⚠️ 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: 0.0854 AC: 12552 AN: 147052 Hom.: 662 Cov.: 0 AF XY: 0.0863 AC XY: 6157 AN XY: 71332

African (AFR) AF: 0.0363 AC: 1461 AN: 40200

American (AMR) AF: 0.0929 AC: 1374 AN: 14784

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 511 AN: 3456

East Asian (EAS) AF: 0.00256 AC: 13 AN: 5074

South Asian (SAS) AF: 0.161 AC: 750 AN: 4666

European-Finnish (FIN) AF: 0.0964 AC: 848 AN: 8794

Middle Eastern (MID) AF: 0.137 AC: 39 AN: 284

European-Non Finnish (NFE) AF: 0.108 AC: 7250 AN: 66854

Other (OTH) AF: 0.114 AC: 232 AN: 2032

Alfa AF: 0.0850 Hom.: 100

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.81
Mutation Taster		=100/0	polymorphism (auto)

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;