11-79395237-T-C

Variant names:

• chr11-79395237-T-C
• rs552604
• NM_001098816.3:c.-321+45272A>G

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+45272A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 152,062 control chromosomes in the GnomAD database, including 8,680 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 0.34 (8680 hom., cov: 33)
• Consequence: TENM4 NM_001098816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0110
• Publications: 2 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 (EAS) allele frequency at 95% confidence interval = 0.36 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.-321+45272A>G		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.-321+45272A>G		intron	N/A	ENSP00000278550.7	Q6N022
	TENM4	ENST00000528688.5	TSL:3	n.239+43725A>G		intron	N/A
	TENM4	ENST00000531583.1	TSL:5	n.440+45272A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51536 AN: 151946 Hom.: 8669 Cov.: 33

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.323

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

GnomAD4 genome AF: 0.339 AC: 51602 AN: 152062 Hom.: 8680 Cov.: 33 AF XY: 0.338 AC XY: 25153 AN XY: 74314

African (AFR) AF: 0.302 AC: 12535 AN: 41482

American (AMR) AF: 0.340 AC: 5196 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1141 AN: 3468

East Asian (EAS) AF: 0.374 AC: 1928 AN: 5156

South Asian (SAS) AF: 0.368 AC: 1776 AN: 4820

European-Finnish (FIN) AF: 0.362 AC: 3820 AN: 10562

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.356 AC: 24171 AN: 67966

Other (OTH) AF: 0.329 AC: 694 AN: 2110

Alfa AF: 0.341 Hom.: 1274

Bravo AF: 0.336

Asia WGS AF: 0.384 AC: 1333 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.4
DANN	Benign	0.53
PhyloP100		-0.011
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: rs552604; hg19: chr11-79106281;