11-79347675-A-G

Variant names:

• chr11-79347675-A-G
• rs1107992
• NM_001098816.3:c.-320-50132T>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.-320-50132T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 151,358 control chromosomes in the GnomAD database, including 4,083 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 (4083 hom., cov: 31)
• Consequence: TENM4 NM_001098816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM4	NM_001098816.3	c.-320-50132T>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.-320-50132T>C		intron_variant	Intron 1 of 33	5	NM_001098816.3	ENSP00000278550.7
TENM4	ENST00000528688.5	n.240-50132T>C		intron_variant	Intron 1 of 3	3
TENM4	ENST00000531583.1	n.441-50132T>C		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31581 AN: 151258 Hom.: 4082 Cov.: 31

Gnomad AFR AF: 0.0502

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.209 AC: 31596 AN: 151358 Hom.: 4083 Cov.: 31 AF XY: 0.214 AC XY: 15839 AN XY: 73940

African (AFR) AF: 0.0502 AC: 2064 AN: 41154

American (AMR) AF: 0.263 AC: 3999 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 950 AN: 3464

East Asian (EAS) AF: 0.319 AC: 1635 AN: 5128

South Asian (SAS) AF: 0.195 AC: 932 AN: 4780

European-Finnish (FIN) AF: 0.385 AC: 4003 AN: 10406

Middle Eastern (MID) AF: 0.227 AC: 65 AN: 286

European-Non Finnish (NFE) AF: 0.254 AC: 17239 AN: 67894

Other (OTH) AF: 0.227 AC: 479 AN: 2106

Alfa AF: 0.237 Hom.: 1746

Bravo AF: 0.196

Asia WGS AF: 0.267 AC: 926 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.0
DANN	Benign	0.73
PhyloP100		1.5
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: rs1107992; hg19: chr11-79058720;