11-79333724-T-C

Variant names:

• chr11-79333724-T-C
• rs512398
• NM_001098816.3:c.-320-36181A>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.-320-36181A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 152,114 control chromosomes in the GnomAD database, including 13,967 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 0.42 (13967 hom., cov: 33)
• Consequence: TENM4 NM_001098816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.226
• Publications: 3 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 (SAS) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM4	NM_001098816.3	c.-320-36181A>G		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.-320-36181A>G		intron_variant	Intron 1 of 33	5	NM_001098816.3	ENSP00000278550.7
TENM4	ENST00000528688.5	n.240-36181A>G		intron_variant	Intron 1 of 3	3
TENM4	ENST00000531583.1	n.441-36181A>G		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64478 AN: 151996 Hom.: 13954 Cov.: 33

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.505

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.424 AC: 64523 AN: 152114 Hom.: 13967 Cov.: 33 AF XY: 0.426 AC XY: 31642 AN XY: 74354

African (AFR) AF: 0.349 AC: 14479 AN: 41490

American (AMR) AF: 0.368 AC: 5622 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1634 AN: 3470

East Asian (EAS) AF: 0.317 AC: 1640 AN: 5170

South Asian (SAS) AF: 0.608 AC: 2931 AN: 4822

European-Finnish (FIN) AF: 0.516 AC: 5456 AN: 10564

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.460 AC: 31286 AN: 67988

Other (OTH) AF: 0.424 AC: 894 AN: 2110

Alfa AF: 0.454 Hom.: 10134

Bravo AF: 0.405

Asia WGS AF: 0.459 AC: 1595 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	0.68
DANN	Benign	0.64
PhyloP100		-0.23
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: rs512398; hg19: chr11-79044769;