rs747970272

Variant names:

• chrX-124381068-C-A
• rs747970272
• ENST00000371130.7:c.7646G>T

Your query was ambiguous. Multiple possible variants found:

• chrX-124381068-C-A
• chrX-124381068-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001163278.2(TENM1):​c.7667G>T​(p.Arg2556Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 23)
• Consequence: TENM1 NM_001163278.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.04

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.885

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM1	NM_001163278.2	c.7667G>T	p.Arg2556Leu	missense_variant	Exon 35 of 35		NP_001156750.1
TENM1	NM_001163279.1	c.7664G>T	p.Arg2555Leu	missense_variant	Exon 32 of 32		NP_001156751.1
TENM1	NM_014253.3	c.7646G>T	p.Arg2549Leu	missense_variant	Exon 31 of 31		NP_055068.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM1	ENST00000371130.7	c.7646G>T	p.Arg2549Leu	missense_variant	Exon 31 of 31	1		ENSP00000360171.3
TENM1	ENST00000422452.3	c.7613G>T	p.Arg2538Leu	missense_variant	Exon 35 of 35	1		ENSP00000403954.4
STAG2	ENST00000469481.1	n.454-30754C>A		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Pathogenic	0.46	D
BayesDel_noAF	Pathogenic	0.43
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T;.
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Pathogenic	0.75	D
MetaRNN	Pathogenic	0.88	D;D
MetaSVM	Uncertain	0.52	D
MutationAssessor	Benign	2.0	M;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-4.0	D;D
REVEL	Pathogenic	0.70
Sift	Benign	0.042	D;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		1.0	D;.
Vest4		0.78
MutPred		0.46		Loss of disorder (P = 0.0825);.;
MVP		0.82
MPC		1.3
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.68
gMVP		0.93

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: rs747970272; hg19: chrX-123514918; COSMIC: COSV100950518;