rs1894516

Variant names:

• chrX-124999772-G-A
• rs1894516
• ENST00000422452.4:c.-64-35955C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000422452.4(TENM1):​c.-64-35955C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 109,815 control chromosomes in the GnomAD database, including 8,155 homozygotes. There are 13,036 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 0.42 (8155 hom., 13036 hem., cov: 22)
• Consequence: TENM1 ENST00000422452.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.278
• Publications: 2 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM1	NM_001163278.2	c.-64-35955C>T		intron_variant	Intron 3 of 34		NP_001156750.1
TENM1	XM_017029208.3	c.-64-35955C>T		intron_variant	Intron 3 of 35		XP_016884697.1
TENM1	XM_017029209.3	c.-119-16423C>T		intron_variant	Intron 3 of 36		XP_016884698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM1	ENST00000422452.4	c.-64-35955C>T		intron_variant	Intron 3 of 34	1		ENSP00000403954.4

Frequencies

GnomAD3 genomes AF: 0.417 AC: 45824 AN: 109767 Hom.: 8154 Cov.: 22

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.353

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.418 AC: 45863 AN: 109815 Hom.: 8155 Cov.: 22 AF XY: 0.404 AC XY: 13036 AN XY: 32273

African (AFR) AF: 0.690 AC: 20895 AN: 30264

American (AMR) AF: 0.272 AC: 2797 AN: 10279

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 847 AN: 2619

East Asian (EAS) AF: 0.120 AC: 420 AN: 3493

South Asian (SAS) AF: 0.285 AC: 740 AN: 2593

European-Finnish (FIN) AF: 0.373 AC: 2150 AN: 5769

Middle Eastern (MID) AF: 0.369 AC: 80 AN: 217

European-Non Finnish (NFE) AF: 0.327 AC: 17161 AN: 52422

Other (OTH) AF: 0.385 AC: 570 AN: 1481

Alfa AF: 0.367 Hom.: 12099

Bravo AF: 0.422

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	7.6
DANN	Benign	0.77
PhyloP100		0.28

Splicing

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

Other links and lift over

dbSNP: rs1894516; hg19: chrX-124133621;