chr11-79360674-T-G

Variant names:

• chr11-79360674-T-G
• rs481975
• NM_001098816.3:c.-320-63131A>C

Variant summary

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

The NM_001098816.3(TENM4):​c.-320-63131A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 152,114 control chromosomes in the GnomAD database, including 40,926 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 0.73 (40926 hom., cov: 33)
• Consequence: TENM4 NM_001098816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0630
• 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: 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM4	NM_001098816.3	c.-320-63131A>C		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.-320-63131A>C		intron_variant	Intron 1 of 33	5	NM_001098816.3	ENSP00000278550.7
TENM4	ENST00000528688.5	n.240-63131A>C		intron_variant	Intron 1 of 3	3
TENM4	ENST00000531583.1	n.441-63131A>C		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.731 AC: 111165 AN: 151996 Hom.: 40900 Cov.: 33

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.778

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.835

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.721

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

GnomAD4 genome AF: 0.731 AC: 111240 AN: 152114 Hom.: 40926 Cov.: 33 AF XY: 0.731 AC XY: 54320 AN XY: 74360

African (AFR) AF: 0.670 AC: 27808 AN: 41478

American (AMR) AF: 0.694 AC: 10611 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.778 AC: 2701 AN: 3472

East Asian (EAS) AF: 0.604 AC: 3111 AN: 5154

South Asian (SAS) AF: 0.652 AC: 3139 AN: 4816

European-Finnish (FIN) AF: 0.835 AC: 8844 AN: 10596

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.773 AC: 52557 AN: 68000

Other (OTH) AF: 0.723 AC: 1525 AN: 2108

Alfa AF: 0.758 Hom.: 8890

Bravo AF: 0.722

Asia WGS AF: 0.652 AC: 2263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.73
PhyloP100		0.063
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: rs481975; hg19: chr11-79071719;