11-78847194-G-T

Variant names:

• chr11-78847194-G-T
• rs547292
• NM_001098816.3:c.1681+6910C>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.1681+6910C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,196 control chromosomes in the GnomAD database, including 4,423 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 0.21 (4423 hom., cov: 33)
• Consequence: TENM4 NM_001098816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620
• 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, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.29 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.1681+6910C>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.1681+6910C>A		intron	N/A	ENSP00000278550.7	Q6N022

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32141 AN: 152078 Hom.: 4424 Cov.: 33

Gnomad AFR AF: 0.0528

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.0521

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.253

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

GnomAD4 genome AF: 0.211 AC: 32142 AN: 152196 Hom.: 4423 Cov.: 33 AF XY: 0.212 AC XY: 15796 AN XY: 74404

African (AFR) AF: 0.0527 AC: 2189 AN: 41548

American (AMR) AF: 0.187 AC: 2859 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1265 AN: 3470

East Asian (EAS) AF: 0.0520 AC: 269 AN: 5172

South Asian (SAS) AF: 0.251 AC: 1211 AN: 4822

European-Finnish (FIN) AF: 0.316 AC: 3343 AN: 10582

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.293 AC: 19935 AN: 67994

Other (OTH) AF: 0.252 AC: 533 AN: 2116

Alfa AF: 0.265 Hom.: 10751

Bravo AF: 0.193

Asia WGS AF: 0.158 AC: 550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.93
DANN	Benign	0.34
PhyloP100		0.062
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: rs547292; hg19: chr11-78558239;