rs12290811

Variant names:

• chr11-79372576-T-A
• rs12290811
• NM_001098816.3:c.-321+67933A>T

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+67933A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,146 control chromosomes in the GnomAD database, including 2,671 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 0.17 (2671 hom., cov: 32)
• Consequence: TENM4 NM_001098816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.294
• Publications: 27 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=-0.61).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM4	NM_001098816.3	c.-321+67933A>T		intron_variant	Intron 1 of 33	ENST00000278550.12	NP_001092286.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM4	ENST00000278550.12	c.-321+67933A>T		intron_variant	Intron 1 of 33	5	NM_001098816.3	ENSP00000278550.7
TENM4	ENST00000528688.5	n.239+66386A>T		intron_variant	Intron 1 of 3	3
TENM4	ENST00000531583.1	n.440+67933A>T		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26320 AN: 152026 Hom.: 2671 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.0945

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0854

Gnomad EAS AF: 0.0553

Gnomad SAS AF: 0.0350

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.173 AC: 26340 AN: 152146 Hom.: 2671 Cov.: 32 AF XY: 0.171 AC XY: 12704 AN XY: 74394

African (AFR) AF: 0.278 AC: 11528 AN: 41484

American (AMR) AF: 0.105 AC: 1602 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0854 AC: 296 AN: 3466

East Asian (EAS) AF: 0.0551 AC: 285 AN: 5176

South Asian (SAS) AF: 0.0359 AC: 173 AN: 4820

European-Finnish (FIN) AF: 0.180 AC: 1911 AN: 10596

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10118 AN: 68004

Other (OTH) AF: 0.144 AC: 305 AN: 2114

Alfa AF: 0.146 Hom.: 977

Bravo AF: 0.175

Asia WGS AF: 0.0530 AC: 182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	9.2
DANN	Benign	0.90
PhyloP100		-0.29
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: rs12290811; hg19: chr11-79083620;