NM_001098816.3:c.1682-7351G>A

Variant names:

• chr11-78821746-C-T
• rs489758
• NM_001098816.3:c.1682-7351G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098816.3(TENM4):​c.1682-7351G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 152,018 control chromosomes in the GnomAD database, including 15,019 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.44 (15019 hom., cov: 33)
• Consequence: TENM4 NM_001098816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740
• Publications: 3 publications found

Genes affected

TENM4 (HGNC:29945): (teneurin transmembrane protein 4) The protein encoded by this gene plays a role in establishing proper neuronal connectivity during development. Defects in this gene have been associated with hereditary essential tremor-5. [provided by RefSeq, Oct 2016]

TENM4 Gene-Disease associations (from GenCC):

• tremor, hereditary essential, 5

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine

ENSG00000308458 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098816.3. 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
	TENM4	NM_001098816.3	MANE Select	c.1682-7351G>A		intron	N/A	NP_001092286.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM4	ENST00000278550.12	TSL:5 MANE Select	c.1682-7351G>A		intron	N/A	ENSP00000278550.7
	ENSG00000308458	ENST00000834204.1		n.211+16227C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66077 AN: 151898 Hom.: 15002 Cov.: 33

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.453

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.435 AC: 66129 AN: 152018 Hom.: 15019 Cov.: 33 AF XY: 0.433 AC XY: 32176 AN XY: 74312

African (AFR) AF: 0.504 AC: 20874 AN: 41448

American (AMR) AF: 0.307 AC: 4693 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1813 AN: 3472

East Asian (EAS) AF: 0.127 AC: 660 AN: 5188

South Asian (SAS) AF: 0.339 AC: 1633 AN: 4822

European-Finnish (FIN) AF: 0.499 AC: 5261 AN: 10552

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.436 AC: 29601 AN: 67944

Other (OTH) AF: 0.449 AC: 948 AN: 2110

Alfa AF: 0.428 Hom.: 7988

Bravo AF: 0.421

Asia WGS AF: 0.251 AC: 872 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.4
DANN	Benign	0.92
PhyloP100		0.074
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: rs489758; hg19: chr11-78532791;