NM_001098816.3:c.-320-55994T>C

Variant names:

• chr11-79353537-A-G
• rs11237798
• NM_001098816.3:c.-320-55994T>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.-320-55994T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,162 control chromosomes in the GnomAD database, including 1,587 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 0.13 (1587 hom., cov: 32)
• Consequence: TENM4 NM_001098816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.426
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM4	NM_001098816.3	c.-320-55994T>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.-320-55994T>C		intron_variant	Intron 1 of 33	5	NM_001098816.3	ENSP00000278550.7
TENM4	ENST00000528688.5	n.240-55994T>C		intron_variant	Intron 1 of 3	3
TENM4	ENST00000531583.1	n.441-55994T>C		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20471 AN: 152044 Hom.: 1581 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.0900

Gnomad SAS AF: 0.0870

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.135 AC: 20505 AN: 152162 Hom.: 1587 Cov.: 32 AF XY: 0.135 AC XY: 10019 AN XY: 74392

African (AFR) AF: 0.220 AC: 9138 AN: 41482

American (AMR) AF: 0.106 AC: 1617 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0248 AC: 86 AN: 3470

East Asian (EAS) AF: 0.0900 AC: 466 AN: 5176

South Asian (SAS) AF: 0.0867 AC: 418 AN: 4822

European-Finnish (FIN) AF: 0.130 AC: 1373 AN: 10588

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7103 AN: 68012

Other (OTH) AF: 0.117 AC: 248 AN: 2112

Alfa AF: 0.102 Hom.: 1447

Bravo AF: 0.136

Asia WGS AF: 0.0970 AC: 338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.9
DANN	Benign	0.42
PhyloP100		-0.43
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: rs11237798; hg19: chr11-79064582;