rs2066918

Variant names:

• chrX-125058599-C-A
• rs2066918
• NM_001163278.2:c.-64-94782G>T

Variant summary

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

The NM_001163278.2(TENM1):​c.-64-94782G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 109,841 control chromosomes in the GnomAD database, including 6,864 homozygotes. There are 10,902 hemizygotes in GnomAD. 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 0.35 (6864 hom., 10902 hem., cov: 22)
• Consequence: TENM1 NM_001163278.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.919
• Publications: 1 publications found

Genes affected

TENM1 (HGNC:8117): (teneurin transmembrane protein 1) The protein encoded by this gene belongs to the tenascin family and teneurin subfamily. It is expressed in the neurons and may function as a cellular signal transducer. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

TENM1 Gene-Disease associations (from GenCC):

• isolated congenital anosmia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• anosmia

  Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics
• cerebral palsy

  Inheritance: XL Classification: LIMITED Submitted by: 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 = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM1	NM_001163278.2	c.-64-94782G>T		intron_variant	Intron 3 of 34	ENST00000422452.4	NP_001156750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM1	ENST00000422452.4	c.-64-94782G>T		intron_variant	Intron 3 of 34	1	NM_001163278.2	ENSP00000403954.4

Frequencies

GnomAD3 genomes AF: 0.349 AC: 38360 AN: 109785 Hom.: 6860 Cov.: 22

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.350 AC: 38418 AN: 109841 Hom.: 6864 Cov.: 22 AF XY: 0.338 AC XY: 10902 AN XY: 32247

African (AFR) AF: 0.698 AC: 21072 AN: 30196

American (AMR) AF: 0.397 AC: 4056 AN: 10218

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 560 AN: 2631

East Asian (EAS) AF: 0.119 AC: 413 AN: 3466

South Asian (SAS) AF: 0.213 AC: 559 AN: 2623

European-Finnish (FIN) AF: 0.189 AC: 1092 AN: 5777

Middle Eastern (MID) AF: 0.305 AC: 64 AN: 210

European-Non Finnish (NFE) AF: 0.190 AC: 9970 AN: 52544

Other (OTH) AF: 0.324 AC: 485 AN: 1498

Alfa AF: 0.270 Hom.: 24678

Bravo AF: 0.380

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.7
DANN	Benign	0.75
PhyloP100		0.92

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2066918; hg19: chrX-124192448;