11-79387057-C-G

Variant names:

• chr11-79387057-C-G
• rs514536
• NM_001098816.3:c.-321+53452G>C

Variant summary

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

The NM_001098816.3(TENM4):​c.-321+53452G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 151,992 control chromosomes in the GnomAD database, including 7,754 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 0.32 (7754 hom., cov: 32)
• Consequence: TENM4 NM_001098816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123
• Publications: 0 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.358 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM4	NM_001098816.3	MANE Select	c.-321+53452G>C		intron	N/A	NP_001092286.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM4	ENST00000278550.12	TSL:5 MANE Select	c.-321+53452G>C		intron	N/A	ENSP00000278550.7
	TENM4	ENST00000528688.5	TSL:3	n.239+51905G>C		intron	N/A
	TENM4	ENST00000531583.1	TSL:5	n.440+53452G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48801 AN: 151874 Hom.: 7746 Cov.: 32

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.321 AC: 48843 AN: 151992 Hom.: 7754 Cov.: 32 AF XY: 0.321 AC XY: 23824 AN XY: 74290

African (AFR) AF: 0.282 AC: 11699 AN: 41430

American (AMR) AF: 0.328 AC: 5012 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1119 AN: 3470

East Asian (EAS) AF: 0.371 AC: 1916 AN: 5158

South Asian (SAS) AF: 0.359 AC: 1728 AN: 4812

European-Finnish (FIN) AF: 0.337 AC: 3557 AN: 10558

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22833 AN: 67980

Other (OTH) AF: 0.307 AC: 647 AN: 2106

Alfa AF: 0.190 Hom.: 386

Bravo AF: 0.319

Asia WGS AF: 0.373 AC: 1296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.4
DANN	Benign	0.66
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs514536; hg19: chr11-79098101;