chrX-124383727-G-C

Variant names:

• chrX-124383727-G-C
• rs748659435
• ENST00000371130.7:c.7183C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001163278.2(TENM1):​c.7204C>G​(p.Gln2402Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: TENM1 NM_001163278.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.94

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]

LOC105373331 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.064976454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM1	NM_001163278.2	c.7204C>G	p.Gln2402Glu	missense_variant	Exon 33 of 35		NP_001156750.1
TENM1	NM_001163279.1	c.7201C>G	p.Gln2401Glu	missense_variant	Exon 30 of 32		NP_001156751.1
TENM1	NM_014253.3	c.7183C>G	p.Gln2395Glu	missense_variant	Exon 29 of 31		NP_055068.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM1	ENST00000371130.7	c.7183C>G	p.Gln2395Glu	missense_variant	Exon 29 of 31	1		ENSP00000360171.3
TENM1	ENST00000422452.3	c.7150C>G	p.Gln2384Glu	missense_variant	Exon 33 of 35	1		ENSP00000403954.4
STAG2	ENST00000469481.1	n.454-28095G>C		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD3 exomes AF: 0.00000546 AC: 1 AN: 183243 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 67781

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000122

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 22

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.7204C>G (p.Q2402E) alteration is located in exon 30 (coding exon 30) of the TENM1 gene. This alteration results from a C to G substitution at nucleotide position 7204, causing the glutamine (Q) at amino acid position 2402 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	11
DANN	Benign	0.85
DEOGEN2	Benign	0.030	T;.
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.84	T;T
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.065	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-1.0	N;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.83	N;N
REVEL	Benign	0.26
Sift	Benign	0.29	T;T
Sift4G	Benign	0.40	T;T
Polyphen		0.0	B;.
Vest4		0.11
MutPred		0.39		Loss of methylation at K2394 (P = 0.0926);.;
MVP		0.39
MPC		0.50
ClinPred		0.045	T
GERP RS		3.8
Varity_R		0.24
gMVP		0.65

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: rs748659435; hg19: chrX-123517577;