rs10521726

Variant names:

• chrX-124533371-G-A
• rs10521726
• NM_001163278.2:c.2652-3388C>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.2652-3388C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0823 in 111,288 control chromosomes in the GnomAD database, including 271 homozygotes. There are 2,696 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 0.082 (271 hom., 2696 hem., cov: 22)
• Consequence: TENM1 NM_001163278.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.95
• Publications: 0 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001163278.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM1	NM_001163278.2	MANE Select	c.2652-3388C>T		intron	N/A	NP_001156750.1	Q9UKZ4-2
	TENM1	NM_001163279.1		c.2649-3388C>T		intron	N/A	NP_001156751.1	B7ZMH4
	TENM1	NM_014253.3		c.2652-3388C>T		intron	N/A	NP_055068.2	Q9UKZ4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM1	ENST00000422452.4	TSL:1 MANE Select	c.2652-3388C>T		intron	N/A	ENSP00000403954.4	Q9UKZ4-2
	TENM1	ENST00000371130.7	TSL:1	c.2652-3388C>T		intron	N/A	ENSP00000360171.3	Q9UKZ4-1

Frequencies

GnomAD3 genomes AF: 0.0823 AC: 9149 AN: 111232 Hom.: 270 Cov.: 22

Gnomad AFR AF: 0.0780

Gnomad AMI AF: 0.0146

Gnomad AMR AF: 0.0580

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.0283

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.122

Gnomad NFE AF: 0.0843

Gnomad OTH AF: 0.0888

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

GnomAD4 genome AF: 0.0823 AC: 9159 AN: 111288 Hom.: 271 Cov.: 22 AF XY: 0.0803 AC XY: 2696 AN XY: 33554

African (AFR) AF: 0.0782 AC: 2395 AN: 30643

American (AMR) AF: 0.0579 AC: 606 AN: 10467

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 391 AN: 2638

East Asian (EAS) AF: 0.0284 AC: 101 AN: 3558

South Asian (SAS) AF: 0.126 AC: 333 AN: 2649

European-Finnish (FIN) AF: 0.117 AC: 694 AN: 5957

Middle Eastern (MID) AF: 0.116 AC: 25 AN: 216

European-Non Finnish (NFE) AF: 0.0843 AC: 4465 AN: 52959

Other (OTH) AF: 0.0917 AC: 139 AN: 1516

Alfa AF: 0.0871 Hom.: 4917

Bravo AF: 0.0788

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.9
DANN	Benign	0.50
PhyloP100		2.0
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: rs10521726; hg19: chrX-123667221;