rs880762

Variant names:

• chr11-79346534-C-T
• rs880762
• NM_001098816.3:c.-320-48991G>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.-320-48991G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 151,916 control chromosomes in the GnomAD database, including 28,506 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 0.60 (28506 hom., cov: 31)
• Consequence: TENM4 NM_001098816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.647
• 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: Laboratory for Molecular Medicine, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.793 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.-320-48991G>A		intron	N/A	NP_001092286.2	Q6N022

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM4	ENST00000278550.12	TSL:5 MANE Select	c.-320-48991G>A		intron	N/A	ENSP00000278550.7	Q6N022
	TENM4	ENST00000528688.5	TSL:3	n.240-48991G>A		intron	N/A
	TENM4	ENST00000531583.1	TSL:5	n.441-48991G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90490 AN: 151798 Hom.: 28464 Cov.: 31

Gnomad AFR AF: 0.800

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.596 AC: 90588 AN: 151916 Hom.: 28506 Cov.: 31 AF XY: 0.588 AC XY: 43664 AN XY: 74234

African (AFR) AF: 0.800 AC: 33135 AN: 41416

American (AMR) AF: 0.478 AC: 7305 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 1864 AN: 3472

East Asian (EAS) AF: 0.281 AC: 1445 AN: 5148

South Asian (SAS) AF: 0.490 AC: 2349 AN: 4792

European-Finnish (FIN) AF: 0.474 AC: 5005 AN: 10570

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.553 AC: 37599 AN: 67942

Other (OTH) AF: 0.564 AC: 1186 AN: 2102

Alfa AF: 0.557 Hom.: 4169

Bravo AF: 0.605

Asia WGS AF: 0.421 AC: 1466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.87
DANN	Benign	0.53
PhyloP100		-0.65
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs880762;

hg19: chr11-79057579;