NM_001098816.3:c.-320-68606T>C

Variant names:

• chr11-79366149-A-G
• rs12576775
• NM_001098816.3:c.-320-68606T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098816.3(TENM4):​c.-320-68606T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 151,918 control chromosomes in the GnomAD database, including 1,727 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 0.15 (1727 hom., cov: 32)
• Consequence: TENM4 NM_001098816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.290
• Publications: 54 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM4	NM_001098816.3	c.-320-68606T>C		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.-320-68606T>C		intron_variant	Intron 1 of 33	5	NM_001098816.3	ENSP00000278550.7
TENM4	ENST00000528688.5	n.240-68606T>C		intron_variant	Intron 1 of 3	3
TENM4	ENST00000531583.1	n.441-68606T>C		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22370 AN: 151802 Hom.: 1728 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.0958

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.0550

Gnomad SAS AF: 0.0674

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.147 AC: 22372 AN: 151918 Hom.: 1727 Cov.: 32 AF XY: 0.146 AC XY: 10819 AN XY: 74242

African (AFR) AF: 0.130 AC: 5398 AN: 41436

American (AMR) AF: 0.107 AC: 1639 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 392 AN: 3470

East Asian (EAS) AF: 0.0545 AC: 281 AN: 5154

South Asian (SAS) AF: 0.0683 AC: 328 AN: 4804

European-Finnish (FIN) AF: 0.196 AC: 2068 AN: 10534

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11852 AN: 67952

Other (OTH) AF: 0.137 AC: 290 AN: 2112

Alfa AF: 0.162 Hom.: 8060

Bravo AF: 0.143

Asia WGS AF: 0.0550 AC: 192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.47
DANN	Benign	0.65
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: rs12576775; hg19: chr11-79077193;