rs501435

Variant names:

• chr11-79162576-C-T
• rs501435
• NM_001098816.3:c.-162-13770G>A

Variant summary

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

The NM_001098816.3(TENM4):​c.-162-13770G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 151,998 control chromosomes in the GnomAD database, including 43,573 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 0.75 (43573 hom., cov: 31)
• Consequence: TENM4 NM_001098816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.810
• Publications: 4 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM4	NM_001098816.3	c.-162-13770G>A		intron_variant	Intron 3 of 33	ENST00000278550.12	NP_001092286.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM4	ENST00000278550.12	c.-162-13770G>A		intron_variant	Intron 3 of 33	5	NM_001098816.3	ENSP00000278550.7

Frequencies

GnomAD3 genomes AF: 0.747 AC: 113391 AN: 151882 Hom.: 43552 Cov.: 31

Gnomad AFR AF: 0.616

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.861

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.862

Gnomad OTH AF: 0.757

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

GnomAD4 genome AF: 0.746 AC: 113450 AN: 151998 Hom.: 43573 Cov.: 31 AF XY: 0.738 AC XY: 54826 AN XY: 74288

African (AFR) AF: 0.615 AC: 25458 AN: 41400

American (AMR) AF: 0.669 AC: 10227 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.861 AC: 2989 AN: 3470

East Asian (EAS) AF: 0.414 AC: 2128 AN: 5138

South Asian (SAS) AF: 0.634 AC: 3048 AN: 4806

European-Finnish (FIN) AF: 0.795 AC: 8404 AN: 10566

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.862 AC: 58617 AN: 68010

Other (OTH) AF: 0.759 AC: 1602 AN: 2112

Alfa AF: 0.823 Hom.: 90142

Bravo AF: 0.730

Asia WGS AF: 0.566 AC: 1970 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.32
DANN	Benign	0.58
PhyloP100		-0.81
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: rs501435; hg19: chr11-78873621;