Genetic Variant TXLNG:p.Gln144Glu (chrX-16820187-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_018360.3(TXLNG):c.430C>G(p.Gln144Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000655 in 1,206,190 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 18 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.000069 ( 0 hom. 18 hem. )

Consequence

TXLNG
NM_018360.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.88

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 18 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXLNG	NM_018360.3 link	c.430C>G	p.Gln144Glu	missense_variant	Exon 3 of 10	ENST00000380122.10	NP_060830.2	Q9NUQ3-1
TXLNG	XM_024452400.2 link	c.313C>G	p.Gln105Glu	missense_variant	Exon 3 of 10		XP_024308168.1
TXLNG	XM_047442249.1 link	c.430C>G	p.Gln144Glu	missense_variant	Exon 3 of 10		XP_047298205.1
TXLNG	NM_001168683.2 link	c.103-7907C>G		intron_variant	Intron 1 of 7		NP_001162154.1	Q9NUQ3-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXLNG	ENST00000380122.10 link	c.430C>G	p.Gln144Glu	missense_variant	Exon 3 of 10	1	NM_018360.3	ENSP00000369465.5		Q9NUQ3-1
TXLNG	ENST00000398155.4 link	c.103-7907C>G		intron_variant	Intron 1 of 7	1		ENSP00000381222.4		Q9NUQ3-2

Frequencies

GnomAD3 genomes

AF:

0.0000269

AC:

AN:

111346

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33552

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000565

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000224

AC:

AN:

178587

Hom.:

AF XY:

0.00

AC XY:

AN XY:

63275

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000498

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000694

AC:

AN:

1094844

Hom.:

Cov.:

AF XY:

0.0000499

AC XY:

AN XY:

360434

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000857

Gnomad4 OTH exome

AF:

0.0000870

GnomAD4 genome

AF:

0.0000269

AC:

AN:

111346

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33552

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000565

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 14, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.430C>G (p.Q144E) alteration is located in exon 3 (coding exon 3) of the TXLNG gene. This alteration results from a C to G substitution at nucleotide position 430, causing the glutamine (Q) at amino acid position 144 to be replaced by a glutamic acid (E). 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

Benign

-0.18

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

1.0

M_CAP

Benign

0.067

MetaRNN

Uncertain

0.56

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.9

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.16

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0060

Polyphen

0.77

Vest4

0.67

MVP

0.28

MPC

0.62

ClinPred

0.53

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.83

gMVP

0.30

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over