11-79123080-A-T

Variant names:

• chr11-79123080-A-T
• rs948763
• NM_001098816.3:c.-66+25630T>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.-66+25630T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 151,888 control chromosomes in the GnomAD database, including 14,663 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 0.44 (14663 hom., cov: 31)
• Consequence: TENM4 NM_001098816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93
• Publications: 2 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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM4	NM_001098816.3	c.-66+25630T>A		intron_variant	Intron 4 of 33	ENST00000278550.12	NP_001092286.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM4	ENST00000278550.12	c.-66+25630T>A		intron_variant	Intron 4 of 33	5	NM_001098816.3	ENSP00000278550.7
TENM4	ENST00000532654.5	n.287+25630T>A		intron_variant	Intron 3 of 4	1
TENM4	ENST00000527736.5	c.-65-53071T>A		intron_variant	Intron 1 of 1	5		ENSP00000433535.1

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66030 AN: 151770 Hom.: 14631 Cov.: 31

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.435 AC: 66122 AN: 151888 Hom.: 14663 Cov.: 31 AF XY: 0.434 AC XY: 32174 AN XY: 74210

African (AFR) AF: 0.362 AC: 14977 AN: 41428

American (AMR) AF: 0.436 AC: 6649 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2065 AN: 3472

East Asian (EAS) AF: 0.398 AC: 2045 AN: 5138

South Asian (SAS) AF: 0.451 AC: 2166 AN: 4800

European-Finnish (FIN) AF: 0.403 AC: 4248 AN: 10532

Middle Eastern (MID) AF: 0.534 AC: 156 AN: 292

European-Non Finnish (NFE) AF: 0.475 AC: 32257 AN: 67954

Other (OTH) AF: 0.464 AC: 977 AN: 2106

Alfa AF: 0.446 Hom.: 1834

Bravo AF: 0.430

Asia WGS AF: 0.448 AC: 1559 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.2
DANN	Benign	0.82
PhyloP100		1.9
Mutation Taster		=98/2	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: rs948763; hg19: chr11-78834125;