chrX-124380627-T-C

Variant names:

• chrX-124380627-T-C
• NM_001163278.2:c.8108A>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001163278.2(TENM1):​c.8108A>G​(p.Tyr2703Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: TENM1 NM_001163278.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.92
• 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]

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]

STAG2 Gene-Disease associations (from GenCC):

• Mullegama-Klein-Martinez syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Illumina, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• Xq25 microduplication syndrome

  Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.901

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.8108A>G	p.Tyr2703Cys	missense	Exon 35 of 35	NP_001156750.1	Q9UKZ4-2
	TENM1	NM_001163279.1		c.8105A>G	p.Tyr2702Cys	missense	Exon 32 of 32	NP_001156751.1	B7ZMH4
	TENM1	NM_014253.3		c.8087A>G	p.Tyr2696Cys	missense	Exon 31 of 31	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.8108A>G	p.Tyr2703Cys	missense	Exon 35 of 35	ENSP00000403954.4	Q9UKZ4-2
	TENM1	ENST00000371130.7	TSL:1	c.8087A>G	p.Tyr2696Cys	missense	Exon 31 of 31	ENSP00000360171.3	Q9UKZ4-1
	STAG2	ENST00000469481.1	TSL:3	n.454-31195T>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D
M_CAP	Pathogenic	0.69	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Uncertain	0.49	D
MutationAssessor	Uncertain	2.6	M
PhyloP100		3.9
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-6.4	D
REVEL	Pathogenic	0.70
Sift	Uncertain	0.015	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.78
MutPred		0.42		Loss of phosphorylation at Y2696 (P = 0.0457)
MVP		0.89
MPC		1.2
ClinPred		0.98	D
GERP RS		5.7
Varity_R		0.78
gMVP		0.64
Mutation Taster		=66/34	polymorphism

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

hg19: chrX-123514477;