Genetic Variant NM_018360.3:c.49G>A (chrX-16786536-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018360.3(TXLNG):c.49G>A(p.Glu17Lys) 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)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

TXLNG
NM_018360.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.13

Publications

0 publications found

Variant links:

Genes affected

TXLNG (HGNC:18578): (taxilin gamma) This gene encodes a member of the taxilin family. The encoded protein binds to the C-terminal coiled-coil region of syntaxin family members 1A, 3A and 4A, and may play a role in intracellular vesicle trafficking. This gene is up-regulated by lipopolysaccharide and the gene product may be involved in cell cycle regulation. The related mouse protein was also shown to inhibit activating transcription factor 4-mediated transcription and thus regulate bone mass accrual. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]

TXLNG links:

ENSG00000301757 (HGNC:):

ENSG00000301757 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25247553).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXLNG	NM_018360.3 link	c.49G>A	p.Glu17Lys	missense_variant	Exon 1 of 10	ENST00000380122.10	NP_060830.2	Q9NUQ3-1
TXLNG	NM_001168683.2 link	c.49G>A	p.Glu17Lys	missense_variant	Exon 1 of 8		NP_001162154.1	Q9NUQ3-2
TXLNG	XM_047442249.1 link	c.49G>A	p.Glu17Lys	missense_variant	Exon 1 of 10		XP_047298205.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TXLNG	ENST00000380122.10 link	c.49G>A	p.Glu17Lys	missense_variant	Exon 1 of 10	1	NM_018360.3	ENSP00000369465.5	Q9NUQ3-1
TXLNG	ENST00000398155.4 link	c.49G>A	p.Glu17Lys	missense_variant	Exon 1 of 8	1		ENSP00000381222.4	Q9NUQ3-2
ENSG00000301757	ENST00000781399.1 link	n.-219C>T		upstream_gene_variant
ENSG00000301757	ENST00000781400.1 link	n.-178C>T		upstream_gene_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

988715

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

311029

African (AFR)

AF:

0.00

AC:

AN:

20981

American (AMR)

AF:

0.00

AC:

AN:

18884

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15431

East Asian (EAS)

AF:

0.00

AC:

AN:

22641

South Asian (SAS)

AF:

0.00

AC:

AN:

42779

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31265

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3569

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

791638

Other (OTH)

AF:

0.00

AC:

AN:

41527

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 28, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.49G>A (p.E17K) alteration is located in exon 1 (coding exon 1) of the TXLNG gene. This alteration results from a G to A substitution at nucleotide position 49, causing the glutamic acid (E) at amino acid position 17 to be replaced by a lysine (K). 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

0.29

BayesDel_addAF

Benign

-0.080

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.064

T;.

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.85

D;D

M_CAP

Pathogenic

0.33

MetaRNN

Benign

0.25

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.55

N;N

PhyloP100

2.1

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.093

Sift

Pathogenic

0.0

D;T

Sift4G

Benign

0.39

T;T

Polyphen

0.97

D;D

Vest4

0.24

MutPred

0.34

Gain of MoRF binding (P = 0.0016);Gain of MoRF binding (P = 0.0016);

MVP

0.47

MPC

0.31

ClinPred

0.63

GERP RS

5.2

PromoterAI

-0.040

Neutral

(source)

Varity_R

0.56

gMVP

0.32

Mutation Taster

=92/8

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over