rs10751301

Variant names:

• chr11-78983593-C-G
• rs10751301
• NM_001098816.3:c.494-80070G>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.494-80070G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 152,152 control chromosomes in the GnomAD database, including 14,984 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 0.41 (14984 hom., cov: 33)
• Consequence: TENM4 NM_001098816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.736 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM4	NM_001098816.3	MANE Select	c.494-80070G>C		intron	N/A	NP_001092286.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM4	ENST00000278550.12	TSL:5 MANE Select	c.494-80070G>C		intron	N/A	ENSP00000278550.7
	TENM4	ENST00000529798.1	TSL:3	n.399+30978G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62968 AN: 152034 Hom.: 14992 Cov.: 33

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.414 AC: 62969 AN: 152152 Hom.: 14984 Cov.: 33 AF XY: 0.419 AC XY: 31132 AN XY: 74382

African (AFR) AF: 0.177 AC: 7341 AN: 41530

American (AMR) AF: 0.518 AC: 7934 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1343 AN: 3470

East Asian (EAS) AF: 0.756 AC: 3896 AN: 5152

South Asian (SAS) AF: 0.590 AC: 2843 AN: 4820

European-Finnish (FIN) AF: 0.529 AC: 5594 AN: 10584

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.482 AC: 32755 AN: 67976

Other (OTH) AF: 0.392 AC: 827 AN: 2112

Alfa AF: 0.441 Hom.: 1957

Bravo AF: 0.405

Asia WGS AF: 0.602 AC: 2090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.77
PhyloP100		-0.086
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: rs10751301; hg19: chr11-78694638; COSMIC: COSV53617271;