rs514536

Variant names:

• chr11-79387057-C-A
• rs514536
• NM_001098816.3:c.-321+53452G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-79387057-C-A
• chr11-79387057-C-G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001098816.3(TENM4):​c.-321+53452G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000395 in 151,940 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000039 (0 hom., cov: 32)
• Consequence: TENM4 NM_001098816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123
• Publications: 0 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BS2: High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM4	NM_001098816.3	c.-321+53452G>T		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.-321+53452G>T		intron_variant	Intron 1 of 33	5	NM_001098816.3	ENSP00000278550.7
TENM4	ENST00000528688.5	n.239+51905G>T		intron_variant	Intron 1 of 3	3
TENM4	ENST00000531583.1	n.440+53452G>T		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.0000395 AC: 6 AN: 151940 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000958

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

GnomAD4 genome AF: 0.0000395 AC: 6 AN: 151940 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74198

African (AFR) AF: 0.00 AC: 0 AN: 41328

American (AMR) AF: 0.000131 AC: 2 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68002

Other (OTH) AF: 0.000958 AC: 2 AN: 2088

Alfa AF: 0.00 Hom.: 386

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.4
DANN	Benign	0.79
PhyloP100		0.12

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: rs514536; hg19: chr11-79098101;