X-124382691-A-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The ENST00000422452.4(TENM1):c.7419T>G(p.Thr2473=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000376 in 1,204,293 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 244 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., 11 hem., cov: 23)
  • Exomes 𝑓: 0.00039 (0 hom. 233 hem.)
• Consequence: TENM1 ENST00000422452.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.288

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]

LOC105373331 (HGNC:):

STAG2 (HGNC:11355): (STAG2 cohesin complex component) The protein encoded by this gene is a subunit of the cohesin complex, which regulates the separation of sister chromatids during cell division. Targeted inactivation of this gene results in chromatid cohesion defects and aneuploidy, suggesting that genetic disruption of cohesin is a cause of aneuploidy in human cancer. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant X-124382691-A-C is Benign according to our data. Variant chrX-124382691-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 3053729.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.288 with no splicing effect.
• BS2: High Hemizygotes in GnomAd at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TENM1	NM_001163278.2	c.7419T>G	p.Thr2473=	synonymous_variant	34/35	ENST00000422452.4
TENM1	XM_017029210.3	c.7518T>G	p.Thr2506=	synonymous_variant	34/35
LOC105373331	XR_938576.1	n.88+1697A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TENM1	ENST00000422452.4	c.7419T>G	p.Thr2473=	synonymous_variant	34/35	1	NM_001163278.2	A1
TENM1	ENST00000371130.7	c.7398T>G	p.Thr2466=	synonymous_variant	30/31	1		P4
STAG2	ENST00000469481.1	n.454-29131A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.000189 AC: 21 AN: 111193 Hom.: 0 Cov.: 23 AF XY: 0.000299 AC XY: 10 AN XY: 33401

Gnomad AFR AF: 0.0000327

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000959

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00561

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000566

Gnomad OTH AF: 0.000671

GnomAD3 exomes AF: 0.000583 AC: 102 AN: 175065 Hom.: 0 AF XY: 0.00104 AC XY: 63 AN XY: 60405

Gnomad AFR exome AF: 0.0000788

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000101

Gnomad OTH exome AF: 0.000234

GnomAD4 exome AF: 0.000394 AC: 431 AN: 1093051 Hom.: 0 Cov.: 28 AF XY: 0.000649 AC XY: 233 AN XY: 359197

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000291

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00619

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000940

Gnomad4 OTH exome AF: 0.000240

GnomAD4 genome AF: 0.000198 AC: 22 AN: 111242 Hom.: 0 Cov.: 23 AF XY: 0.000329 AC XY: 11 AN XY: 33460

Gnomad4 AFR AF: 0.0000326

Gnomad4 AMR AF: 0.0000958

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00601

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000566

Gnomad4 OTH AF: 0.000663

Alfa AF: 0.000162 Hom.: 1

Bravo AF: 0.0000416

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

TENM1-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 24, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	6.2
Dann	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs202013155; hg19: chrX-123516541;