chr5-168246948-C-T

Variant names:

• chr5-168246948-C-T
• rs74464871
• NM_001395460.1:c.6009C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001395460.1(TENM2):​c.6009C>T​(p.Asp2003Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00231 in 1,613,932 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (42 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (29 hom.)
• Consequence: TENM2 NM_001395460.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.814
• Publications: 3 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]

TENM2-AS1 (HGNC:56066): (TENM2 antisense RNA 2)

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 5-168246948-C-T is Benign according to our data. Variant chr5-168246948-C-T is described in ClinVar as Benign. ClinVar VariationId is 780964.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.814 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0121 (1840/152232) while in subpopulation AFR AF = 0.0408 (1694/41524). AF 95% confidence interval is 0.0392. There are 42 homozygotes in GnomAd4. There are 884 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1840 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.6009C>T	p.Asp2003Asp	synonymous	Exon 29 of 31	NP_001382389.1	Q9NT68-1
	TENM2	NM_001122679.2		c.5982C>T	p.Asp1994Asp	synonymous	Exon 28 of 30	NP_001116151.1
	TENM2	NM_001368145.1		c.5532C>T	p.Asp1844Asp	synonymous	Exon 25 of 27	NP_001355074.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM2	ENST00000518659.6	TSL:5 MANE Select	c.6009C>T	p.Asp2003Asp	synonymous	Exon 29 of 31	ENSP00000429430.1	Q9NT68-1
	TENM2	ENST00000520394.5	TSL:1	c.5292C>T	p.Asp1764Asp	synonymous	Exon 23 of 25	ENSP00000427874.1	F8VNQ3
	TENM2	ENST00000519204.5	TSL:5	c.5646C>T	p.Asp1882Asp	synonymous	Exon 26 of 28	ENSP00000428964.1	G3V106

Frequencies

GnomAD3 genomes AF: 0.0120 AC: 1831 AN: 152114 Hom.: 40 Cov.: 32

Gnomad AFR AF: 0.0407

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0120

GnomAD2 exomes AF: 0.00310 AC: 773 AN: 249258 AF XY: 0.00224

Gnomad AFR exome AF: 0.0423

Gnomad AMR exome AF: 0.00226

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.000257

Gnomad OTH exome AF: 0.00149

GnomAD4 exome AF: 0.00129 AC: 1892 AN: 1461700 Hom.: 29 Cov.: 31 AF XY: 0.00108 AC XY: 787 AN XY: 727130

African (AFR) AF: 0.0413 AC: 1383 AN: 33480

American (AMR) AF: 0.00230 AC: 103 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53400

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5768

European-Non Finnish (NFE) AF: 0.000162 AC: 180 AN: 1111862

Other (OTH) AF: 0.00346 AC: 209 AN: 60372

GnomAD4 genome AF: 0.0121 AC: 1840 AN: 152232 Hom.: 42 Cov.: 32 AF XY: 0.0119 AC XY: 884 AN XY: 74426

African (AFR) AF: 0.0408 AC: 1694 AN: 41524

American (AMR) AF: 0.00648 AC: 99 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68028

Other (OTH) AF: 0.0119 AC: 25 AN: 2108

Alfa AF: 0.0112 Hom.: 14

Bravo AF: 0.0142

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	1.8
DANN	Benign	0.74
PhyloP100		-0.81
Mutation Taster		=86/14	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: rs74464871; hg19: chr5-167673953;