Genetic Variant TXLNG:p.Ala333Val (chrX-16834296-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_018360.3(TXLNG):c.998C>T(p.Ala333Val) variant causes a missense change. The variant allele was found at a frequency of 0.000022 in 1,092,572 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. 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: 0.000022 ( 0 hom. 6 hem. )

Consequence

TXLNG
NM_018360.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.58

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.26412445).

BS2

High Hemizygotes in GnomAdExome4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXLNG	NM_018360.3 link	c.998C>T	p.Ala333Val	missense_variant	Exon 7 of 10	ENST00000380122.10	NP_060830.2	Q9NUQ3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXLNG	ENST00000380122.10 link	c.998C>T	p.Ala333Val	missense_variant	Exon 7 of 10	1	NM_018360.3	ENSP00000369465.5		Q9NUQ3-1
TXLNG	ENST00000398155.4 link	c.602C>T	p.Ala201Val	missense_variant	Exon 5 of 8	1		ENSP00000381222.4		Q9NUQ3-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000562

AC:

AN:

177787

AF XY:

0.0000160

show subpopulations

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000124

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000220

AC:

AN:

1092572

Hom.:

Cov.:

AF XY:

0.0000167

AC XY:

AN XY:

358412

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26280

American (AMR)

AF:

0.00

AC:

AN:

34592

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19256

East Asian (EAS)

AF:

0.00

AC:

AN:

30017

South Asian (SAS)

AF:

0.00

AC:

AN:

52694

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40457

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4117

European-Non Finnish (NFE)

AF:

0.0000262

AC:

AN:

839294

Other (OTH)

AF:

0.0000436

AC:

AN:

45865

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.439

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000540

Hom.:

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 09, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.998C>T (p.A333V) alteration is located in exon 7 (coding exon 7) of the TXLNG gene. This alteration results from a C to T substitution at nucleotide position 998, causing the alanine (A) at amino acid position 333 to be replaced by a valine (V). 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

0.31

BayesDel_addAF

Uncertain

0.026

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;.

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.83

T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.26

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

M;.

PhyloP100

5.6

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-3.5

D;D

REVEL

Benign

0.16

Sift

Benign

0.22

T;T

Sift4G

Benign

0.10

T;T

Polyphen

0.37

B;B

Vest4

0.54

MutPred

0.59

Gain of methylation at K331 (P = 0.0865);.;

MVP

0.66

MPC

0.30

ClinPred

0.81

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.67

gMVP

0.52

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

X-16834296-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over