11-79281641-T-C

Variant names:

• chr11-79281641-T-C
• rs1151200
• NM_001098816.3:c.-265+15847A>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.-265+15847A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 151,912 control chromosomes in the GnomAD database, including 19,379 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 0.50 (19379 hom., cov: 31)
• Consequence: TENM4 NM_001098816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270
• Publications: 6 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 (EAS) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM4	NM_001098816.3	c.-265+15847A>G		intron_variant	Intron 2 of 33	ENST00000278550.12	NP_001092286.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM4	ENST00000278550.12	c.-265+15847A>G		intron_variant	Intron 2 of 33	5	NM_001098816.3	ENSP00000278550.7
TENM4	ENST00000528688.5	n.295+15847A>G		intron_variant	Intron 2 of 3	3
TENM4	ENST00000531583.1	n.496+15847A>G		intron_variant	Intron 2 of 4	5

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75847 AN: 151794 Hom.: 19359 Cov.: 31

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.497

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

GnomAD4 genome AF: 0.500 AC: 75908 AN: 151912 Hom.: 19379 Cov.: 31 AF XY: 0.508 AC XY: 37695 AN XY: 74238

African (AFR) AF: 0.582 AC: 24095 AN: 41434

American (AMR) AF: 0.440 AC: 6717 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 1574 AN: 3464

East Asian (EAS) AF: 0.676 AC: 3474 AN: 5138

South Asian (SAS) AF: 0.575 AC: 2765 AN: 4806

European-Finnish (FIN) AF: 0.586 AC: 6191 AN: 10566

Middle Eastern (MID) AF: 0.551 AC: 161 AN: 292

European-Non Finnish (NFE) AF: 0.436 AC: 29582 AN: 67918

Other (OTH) AF: 0.494 AC: 1041 AN: 2108

Alfa AF: 0.460 Hom.: 27839

Bravo AF: 0.487

Asia WGS AF: 0.596 AC: 2072 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	2.8
DANN	Benign	0.31
PhyloP100		-0.027
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: rs1151200; hg19: chr11-78992686;