11-79412839-C-T

Variant names:

• chr11-79412839-C-T
• rs2175420
• NM_001098816.3:c.-321+27670G>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.-321+27670G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,160 control chromosomes in the GnomAD database, including 2,342 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 (2342 hom., cov: 33)
• Consequence: TENM4 NM_001098816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82
• Publications: 8 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 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.-321+27670G>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.-321+27670G>A		intron	N/A	ENSP00000278550.7
	TENM4	ENST00000528688.5	TSL:3	n.239+26123G>A		intron	N/A
	TENM4	ENST00000531583.1	TSL:5	n.440+27670G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25922 AN: 152042 Hom.: 2344 Cov.: 33

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.0659

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.170 AC: 25925 AN: 152160 Hom.: 2342 Cov.: 33 AF XY: 0.165 AC XY: 12289 AN XY: 74416

African (AFR) AF: 0.187 AC: 7771 AN: 41478

American (AMR) AF: 0.141 AC: 2153 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 804 AN: 3470

East Asian (EAS) AF: 0.0660 AC: 342 AN: 5178

South Asian (SAS) AF: 0.110 AC: 531 AN: 4826

European-Finnish (FIN) AF: 0.105 AC: 1115 AN: 10602

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12467 AN: 68004

Other (OTH) AF: 0.172 AC: 363 AN: 2108

Alfa AF: 0.171 Hom.: 444

Bravo AF: 0.175

Asia WGS AF: 0.102 AC: 356 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	0.20
DANN	Benign	0.25
PhyloP100		-1.8
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: rs2175420; hg19: chr11-79123883;