rs10521728

Variant names:

• chrX-124952607-C-G
• rs10521728
• ENST00000422452.4:c.217+10930G>C

Variant summary

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

The ENST00000422452.4(TENM1):​c.217+10930G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.059 in 110,938 control chromosomes in the GnomAD database, including 388 homozygotes. There are 1,755 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 0.059 (388 hom., 1755 hem., cov: 22)
• Consequence: TENM1 ENST00000422452.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM1	NM_001163278.2	c.217+10930G>C		intron_variant	Intron 4 of 34		NP_001156750.1
TENM1	NM_001163279.1	c.217+10930G>C		intron_variant	Intron 1 of 31		NP_001156751.1
TENM1	NM_014253.3	c.217+10930G>C		intron_variant	Intron 1 of 30		NP_055068.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM1	ENST00000422452.4	c.217+10930G>C		intron_variant	Intron 4 of 34	1		ENSP00000403954.4
TENM1	ENST00000371130.7	c.217+10930G>C		intron_variant	Intron 1 of 30	1		ENSP00000360171.3

Frequencies

GnomAD3 genomes AF: 0.0588 AC: 6525 AN: 110887 Hom.: 387 Cov.: 22

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0427

Gnomad ASJ AF: 0.0459

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00151

Gnomad FIN AF: 0.000502

Gnomad MID AF: 0.0717

Gnomad NFE AF: 0.00482

Gnomad OTH AF: 0.0735

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

GnomAD4 genome AF: 0.0590 AC: 6543 AN: 110938 Hom.: 388 Cov.: 22 AF XY: 0.0528 AC XY: 1755 AN XY: 33230

African (AFR) AF: 0.184 AC: 5590 AN: 30452

American (AMR) AF: 0.0427 AC: 444 AN: 10410

Ashkenazi Jewish (ASJ) AF: 0.0459 AC: 121 AN: 2636

East Asian (EAS) AF: 0.00 AC: 0 AN: 3511

South Asian (SAS) AF: 0.00151 AC: 4 AN: 2648

European-Finnish (FIN) AF: 0.000502 AC: 3 AN: 5981

Middle Eastern (MID) AF: 0.0787 AC: 17 AN: 216

European-Non Finnish (NFE) AF: 0.00482 AC: 255 AN: 52897

Other (OTH) AF: 0.0726 AC: 109 AN: 1501

Alfa AF: 0.0381 Hom.: 186

Bravo AF: 0.0714

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.76
PhyloP100		1.2
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: rs10521728; hg19: chrX-124086456;