chrX-124382691-A-C

Variant names:

• chrX-124382691-A-C
• rs202013155
• NM_001163278.2:c.7419T>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_001163278.2(TENM1):​c.7419T>G​(p.Thr2473Thr) 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 (no stars).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., 11 hem., cov: 23)
  • Exomes 𝑓: 0.00039 (0 hom. 233 hem.)
• Consequence: TENM1 NM_001163278.2 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.288
• 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

LOC105373331 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 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 VariationId is 3053729.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.288 with no splicing effect.
• BS2: High AC in GnomAd4 at 22 XL,AD gene.

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.7419T>G	p.Thr2473Thr	synonymous	Exon 34 of 35	NP_001156750.1	Q9UKZ4-2
	TENM1	NM_001163279.1		c.7416T>G	p.Thr2472Thr	synonymous	Exon 31 of 32	NP_001156751.1	B7ZMH4
	TENM1	NM_014253.3		c.7398T>G	p.Thr2466Thr	synonymous	Exon 30 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.7419T>G	p.Thr2473Thr	synonymous	Exon 34 of 35	ENSP00000403954.4	Q9UKZ4-2
	TENM1	ENST00000371130.7	TSL:1	c.7398T>G	p.Thr2466Thr	synonymous	Exon 30 of 31	ENSP00000360171.3	Q9UKZ4-1
	STAG2	ENST00000469481.1	TSL:3	n.454-29131A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000189 AC: 21 AN: 111193 Hom.: 0 Cov.: 23

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

GnomAD2 exomes AF: 0.000583 AC: 102 AN: 175065 AF XY: 0.00104

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 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

African (AFR) AF: 0.00 AC: 0 AN: 26165

American (AMR) AF: 0.0000291 AC: 1 AN: 34336

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19252

East Asian (EAS) AF: 0.00 AC: 0 AN: 29884

South Asian (SAS) AF: 0.00619 AC: 327 AN: 52789

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40471

Middle Eastern (MID) AF: 0.00316 AC: 13 AN: 4116

European-Non Finnish (NFE) AF: 0.0000940 AC: 79 AN: 840155

Other (OTH) AF: 0.000240 AC: 11 AN: 45883

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

African (AFR) AF: 0.0000326 AC: 1 AN: 30690

American (AMR) AF: 0.0000958 AC: 1 AN: 10436

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2645

East Asian (EAS) AF: 0.00 AC: 0 AN: 3565

South Asian (SAS) AF: 0.00601 AC: 16 AN: 2663

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5831

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.0000566 AC: 3 AN: 53001

Other (OTH) AF: 0.000663 AC: 1 AN: 1509

Alfa AF: 0.000162 Hom.: 1

Bravo AF: 0.0000416

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	TENM1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	6.2
DANN	Benign	0.70
PhyloP100		0.29
Mutation Taster		=71/29	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: rs202013155; hg19: chrX-123516541;