11-79066002-C-T

Variant names:

• chr11-79066002-C-T
• rs7937442
• NM_001098816.3:c.224-995G>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.224-995G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.904 in 152,210 control chromosomes in the GnomAD database, including 62,614 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 0.90 (62614 hom., cov: 33)
• Consequence: TENM4 NM_001098816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.52
• Publications: 1 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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.95 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.224-995G>A		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.224-995G>A		intron	N/A	ENSP00000278550.7
	TENM4	ENST00000532654.5	TSL:1	n.576-995G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.904 AC: 137524 AN: 152090 Hom.: 62579 Cov.: 33

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.967

Gnomad AMR AF: 0.831

Gnomad ASJ AF: 0.959

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.935

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.956

Gnomad OTH AF: 0.915

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

GnomAD4 genome AF: 0.904 AC: 137613 AN: 152210 Hom.: 62614 Cov.: 33 AF XY: 0.901 AC XY: 67038 AN XY: 74406

African (AFR) AF: 0.873 AC: 36212 AN: 41486

American (AMR) AF: 0.831 AC: 12714 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.959 AC: 3329 AN: 3472

East Asian (EAS) AF: 0.639 AC: 3306 AN: 5174

South Asian (SAS) AF: 0.827 AC: 3986 AN: 4820

European-Finnish (FIN) AF: 0.935 AC: 9919 AN: 10604

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.956 AC: 65054 AN: 68026

Other (OTH) AF: 0.909 AC: 1921 AN: 2114

Alfa AF: 0.930 Hom.: 31383

Bravo AF: 0.893

Asia WGS AF: 0.712 AC: 2478 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.012
DANN	Benign	0.63
PhyloP100		-2.5
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: rs7937442; hg19: chr11-78777047;