X-124562798-G-C

Variant names:

• chrX-124562798-G-C
• rs2843525
• NM_001163278.2:c.2287+951C>G

Variant summary

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

The NM_001163278.2(TENM1):​c.2287+951C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 110,919 control chromosomes in the GnomAD database, including 8,165 homozygotes. There are 14,177 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 (8165 hom., 14177 hem., cov: 23)
• Consequence: TENM1 NM_001163278.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.712
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM1	NM_001163278.2	c.2287+951C>G		intron_variant	Intron 16 of 34	ENST00000422452.4	NP_001156750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM1	ENST00000422452.4	c.2287+951C>G		intron_variant	Intron 16 of 34	1	NM_001163278.2	ENSP00000403954.4
TENM1	ENST00000371130.7	c.2287+951C>G		intron_variant	Intron 13 of 30	1		ENSP00000360171.3

Frequencies

GnomAD3 genomes AF: 0.424 AC: 46960 AN: 110860 Hom.: 8159 Cov.: 23

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.810

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.216

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.424 AC: 47024 AN: 110919 Hom.: 8165 Cov.: 23 AF XY: 0.427 AC XY: 14177 AN XY: 33227

African (AFR) AF: 0.645 AC: 19647 AN: 30482

American (AMR) AF: 0.404 AC: 4239 AN: 10486

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 790 AN: 2637

East Asian (EAS) AF: 0.810 AC: 2814 AN: 3476

South Asian (SAS) AF: 0.571 AC: 1515 AN: 2654

European-Finnish (FIN) AF: 0.360 AC: 2117 AN: 5875

Middle Eastern (MID) AF: 0.226 AC: 48 AN: 212

European-Non Finnish (NFE) AF: 0.285 AC: 15062 AN: 52900

Other (OTH) AF: 0.383 AC: 582 AN: 1520

Alfa AF: 0.205 Hom.: 977

Bravo AF: 0.436

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.10
DANN	Benign	0.42
PhyloP100		-0.71
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: rs2843525; hg19: chrX-123696648;