X-124380732-T-G

Position:

• chrX-124380732-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP2 BP4

The NM_001163278.2(TENM1):​c.8003A>C​(p.Lys2668Thr) 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. 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: 3.06

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), TENM1. . Gene score misZ 3.4329 (greater than the threshold 3.09). GenCC has associacion of gene with anosmia, cerebral palsy, isolated congenital anosmia.
• BP4: Computational evidence support a benign effect (MetaRNN=0.38520613).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TENM1	NM_001163278.2	c.8003A>C	p.Lys2668Thr	missense_variant	35/35		NP_001156750.1
TENM1	NM_001163279.1	c.8000A>C	p.Lys2667Thr	missense_variant	32/32		NP_001156751.1
TENM1	NM_014253.3	c.7982A>C	p.Lys2661Thr	missense_variant	31/31		NP_055068.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TENM1	ENST00000371130.7	c.7982A>C	p.Lys2661Thr	missense_variant	31/31	1		ENSP00000360171.3
TENM1	ENST00000422452.3	c.7949A>C	p.Lys2650Thr	missense_variant	35/35	1		ENSP00000403954.4
STAG2	ENST00000469481.1	n.454-31090T>G		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 05, 2024

The c.8003A>C (p.K2668T) alteration is located in exon 32 (coding exon 32) of the TENM1 gene. This alteration results from a A to C substitution at nucleotide position 8003, causing the lysine (K) at amino acid position 2668 to be replaced by a threonine (T). 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	0.13
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.061	T;.
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Pathogenic	0.46	D
MetaRNN	Benign	0.39	T;T
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Benign	1.7	L;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-2.5	D;D
REVEL	Uncertain	0.41
Sift	Uncertain	0.020	D;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.22	B;.
Vest4		0.36
MutPred		0.35		Loss of ubiquitination at K2661 (P = 0.0161);.;
MVP		0.79
MPC		0.57
ClinPred		0.74	D
GERP RS		5.7
Varity_R		0.43
gMVP		0.57

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-123514582;