11-79354056-C-T

Variant names:

• chr11-79354056-C-T
• rs530965
• NM_001098816.3:c.-320-56513G>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.-320-56513G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 152,096 control chromosomes in the GnomAD database, including 17,667 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 0.48 (17667 hom., cov: 34)
• Consequence: TENM4 NM_001098816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.822
• Publications: 13 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM4	NM_001098816.3	c.-320-56513G>A		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.-320-56513G>A		intron_variant	Intron 1 of 33	5	NM_001098816.3	ENSP00000278550.7
TENM4	ENST00000528688.5	n.240-56513G>A		intron_variant	Intron 1 of 3	3
TENM4	ENST00000531583.1	n.441-56513G>A		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72744 AN: 151978 Hom.: 17637 Cov.: 34

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.455

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

GnomAD4 genome AF: 0.479 AC: 72834 AN: 152096 Hom.: 17667 Cov.: 34 AF XY: 0.483 AC XY: 35931 AN XY: 74374

African (AFR) AF: 0.457 AC: 18969 AN: 41490

American (AMR) AF: 0.451 AC: 6892 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1288 AN: 3468

East Asian (EAS) AF: 0.448 AC: 2315 AN: 5166

South Asian (SAS) AF: 0.369 AC: 1776 AN: 4818

European-Finnish (FIN) AF: 0.650 AC: 6882 AN: 10586

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

European-Non Finnish (NFE) AF: 0.490 AC: 33326 AN: 67978

Other (OTH) AF: 0.456 AC: 964 AN: 2112

Alfa AF: 0.477 Hom.: 49431

Bravo AF: 0.468

Asia WGS AF: 0.422 AC: 1464 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.6
DANN	Benign	0.28
PhyloP100		0.82
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: rs530965; hg19: chr11-79065101;