11-79049428-T-C

Variant names:

• chr11-79049428-T-C
• rs1369458
• NM_001098816.3:c.493+15310A>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.493+15310A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,198 control chromosomes in the GnomAD database, including 1,466 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 (1466 hom., cov: 34)
• Consequence: TENM4 NM_001098816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.696
• Publications: 9 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM4	NM_001098816.3	c.493+15310A>G		intron_variant	Intron 6 of 33	ENST00000278550.12	NP_001092286.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM4	ENST00000278550.12	c.493+15310A>G		intron_variant	Intron 6 of 33	5	NM_001098816.3	ENSP00000278550.7

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20082 AN: 152080 Hom.: 1466 Cov.: 34

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.0648

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.0998

Gnomad EAS AF: 0.0993

Gnomad SAS AF: 0.0674

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.132 AC: 20098 AN: 152198 Hom.: 1466 Cov.: 34 AF XY: 0.130 AC XY: 9692 AN XY: 74408

African (AFR) AF: 0.183 AC: 7581 AN: 41534

American (AMR) AF: 0.127 AC: 1942 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0998 AC: 346 AN: 3468

East Asian (EAS) AF: 0.0995 AC: 515 AN: 5174

South Asian (SAS) AF: 0.0669 AC: 322 AN: 4816

European-Finnish (FIN) AF: 0.134 AC: 1417 AN: 10588

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7588 AN: 68008

Other (OTH) AF: 0.140 AC: 295 AN: 2112

Alfa AF: 0.117 Hom.: 2085

Bravo AF: 0.136

Asia WGS AF: 0.100 AC: 349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.56
DANN	Benign	0.59
PhyloP100		-0.70
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: rs1369458; hg19: chr11-78760473;