X-124381090-C-T

Position:

• chrX-124381090-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_001163278.2(TENM1):​c.7645G>A​(p.Val2549Ile) 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. 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: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.08

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 1 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=0.14527035).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TENM1	NM_001163278.2	c.7645G>A	p.Val2549Ile	missense_variant	35/35		NP_001156750.1
TENM1	NM_001163279.1	c.7642G>A	p.Val2548Ile	missense_variant	32/32		NP_001156751.1
TENM1	NM_014253.3	c.7624G>A	p.Val2542Ile	missense_variant	31/31		NP_055068.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TENM1	ENST00000371130.7	c.7624G>A	p.Val2542Ile	missense_variant	31/31	1		ENSP00000360171.3
TENM1	ENST00000422452.3	c.7591G>A	p.Val2531Ile	missense_variant	35/35	1		ENSP00000403954.4
STAG2	ENST00000469481.1	n.454-30732C>T		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

Sep 10, 2024

The c.7645G>A (p.V2549I) alteration is located in exon 32 (coding exon 32) of the TENM1 gene. This alteration results from a G to A substitution at nucleotide position 7645, causing the valine (V) at amino acid position 2549 to be replaced by an isoleucine (I). 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	0.087
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	24
DANN	Benign	0.95
DEOGEN2	Benign	0.028	T;.
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Pathogenic	0.53	D
MetaRNN	Benign	0.15	T;T
MetaSVM	Uncertain	0.12	D
MutationAssessor	Benign	0.64	N;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.33	N;N
REVEL	Uncertain	0.31
Sift	Benign	0.72	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.93	P;.
Vest4		0.16
MutPred		0.25		Gain of helix (P = 0.062);.;
MVP		0.53
MPC		0.39
ClinPred		0.41	T
GERP RS		5.8
Varity_R		0.21
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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-123514940;