chr11-79361733-T-C

Variant names:

• chr11-79361733-T-C
• rs546868
• NM_001098816.3:c.-320-64190A>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.-320-64190A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.776 in 152,092 control chromosomes in the GnomAD database, including 46,095 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 0.78 (46095 hom., cov: 32)
• Consequence: TENM4 NM_001098816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.533
• Publications: 1 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: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Ambry Genetics

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 (AFR) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098816.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM4	NM_001098816.3	MANE Select	c.-320-64190A>G		intron	N/A	NP_001092286.2	Q6N022

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM4	ENST00000278550.12	TSL:5 MANE Select	c.-320-64190A>G		intron	N/A	ENSP00000278550.7	Q6N022
	TENM4	ENST00000528688.5	TSL:3	n.240-64190A>G		intron	N/A
	TENM4	ENST00000531583.1	TSL:5	n.441-64190A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.776 AC: 117963 AN: 151974 Hom.: 46044 Cov.: 32

Gnomad AFR AF: 0.822

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.710

Gnomad ASJ AF: 0.789

Gnomad EAS AF: 0.604

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.835

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.774

Gnomad OTH AF: 0.758

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

GnomAD4 genome AF: 0.776 AC: 118077 AN: 152092 Hom.: 46095 Cov.: 32 AF XY: 0.775 AC XY: 57644 AN XY: 74366

African (AFR) AF: 0.822 AC: 34103 AN: 41464

American (AMR) AF: 0.710 AC: 10855 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.789 AC: 2739 AN: 3472

East Asian (EAS) AF: 0.604 AC: 3119 AN: 5166

South Asian (SAS) AF: 0.680 AC: 3280 AN: 4824

European-Finnish (FIN) AF: 0.835 AC: 8834 AN: 10580

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.774 AC: 52591 AN: 67988

Other (OTH) AF: 0.760 AC: 1607 AN: 2114

Alfa AF: 0.767 Hom.: 15729

Bravo AF: 0.773

Asia WGS AF: 0.676 AC: 2347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.25
DANN	Benign	0.44
PhyloP100		-0.53
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: rs546868; hg19: chr11-79072778;