Genetic Variant TXLNG:p.Ile187Thr (chrX-16828155-T-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_018360.3(TXLNG):c.560T>C(p.Ile187Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000182 in 1,097,350 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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: 0.0000018 ( 0 hom. 0 hem. )

Consequence

TXLNG
NM_018360.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.27

Publications

1 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: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28944263).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXLNG	NM_018360.3 link	c.560T>C	p.Ile187Thr	missense_variant	Exon 4 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.560T>C	p.Ile187Thr	missense_variant	Exon 4 of 10	1	NM_018360.3	ENSP00000369465.5		Q9NUQ3-1
TXLNG	ENST00000398155.4 link	c.164T>C	p.Ile55Thr	missense_variant	Exon 2 of 8	1		ENSP00000381222.4		Q9NUQ3-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000547

AC:

AN:

182948

AF XY:

0.00

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:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000182

AC:

AN:

1097350

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

362736

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26389

American (AMR)

AF:

0.00

AC:

AN:

35183

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19344

East Asian (EAS)

AF:

0.00

AC:

AN:

30186

South Asian (SAS)

AF:

0.00

AC:

AN:

53986

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40504

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4129

European-Non Finnish (NFE)

AF:

0.00000238

AC:

AN:

841581

Other (OTH)

AF:

0.00

AC:

AN:

46048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 15, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.560T>C (p.I187T) alteration is located in exon 4 (coding exon 4) of the TXLNG gene. This alteration results from a T to C substitution at nucleotide position 560, causing the isoleucine (I) at amino acid position 187 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

0.15

BayesDel_addAF

Benign

-0.097

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

T;.

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.83

T;T

M_CAP

Uncertain

0.097

MetaRNN

Benign

0.29

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

L;.

PhyloP100

6.3

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-3.4

D;D

REVEL

Benign

0.18

Sift

Benign

0.18

T;D

Sift4G

Benign

0.13

T;T

Polyphen

0.20

B;B

Vest4

0.49

MutPred

0.60

Loss of methylation at K189 (P = 0.055);.;

MVP

0.30

MPC

0.53

ClinPred

0.36

GERP RS

5.4

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.48

gMVP

0.36

Mutation Taster

=72/28

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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X-16828155-T-C

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