Variant X-16818725-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_018360.3(TXLNG):c.254G>C(p.Gly85Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,210,386 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 13 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000024 ( 0 hom. 13 hem. )

Consequence

TXLNG
NM_018360.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.747

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.023551285).

BS2

High Hemizygotes in GnomAdExome4 at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TXLNG	NM_018360.3 linkuse as main transcript	c.254G>C	p.Gly85Ala	missense_variant	2/10	ENST00000380122.10	NP_060830.2
TXLNG	XM_024452400.2 linkuse as main transcript	c.137G>C	p.Gly46Ala	missense_variant	2/10		XP_024308168.1
TXLNG	XM_047442249.1 linkuse as main transcript	c.254G>C	p.Gly85Ala	missense_variant	2/10		XP_047298205.1
TXLNG	NM_001168683.2 linkuse as main transcript	c.103-9369G>C		intron_variant			NP_001162154.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TXLNG	ENST00000380122.10 linkuse as main transcript	c.254G>C	p.Gly85Ala	missense_variant	2/10	1	NM_018360.3	ENSP00000369465	P1	Q9NUQ3-1
TXLNG	ENST00000398155.4 linkuse as main transcript	c.103-9369G>C		intron_variant		1		ENSP00000381222		Q9NUQ3-2

Frequencies

GnomAD3 genomes

AF:

0.00000892

AC:

AN:

112140

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34304

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:

0.000364

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000655

AC:

AN:

183312

Hom.:

AF XY:

0.0000738

AC XY:

AN XY:

67790

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000722

Gnomad SAS exome

AF:

0.000524

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.0000237

AC:

AN:

1098246

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

363600

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.000425

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

AF:

0.00000892

AC:

AN:

112140

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34304

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:

0.000364

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000102

Hom.:

ExAC

AF:

0.000123

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 29, 2022

The c.254G>C (p.G85A) alteration is located in exon 2 (coding exon 2) of the TXLNG gene. This alteration results from a G to C substitution at nucleotide position 254, causing the glycine (G) at amino acid position 85 to be replaced by an alanine (A). 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

0.077

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.060

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.77

M_CAP

Benign

0.010

MetaRNN

Benign

0.024

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.56

REVEL

Benign

0.0090

Sift

Benign

0.43

Sift4G

Benign

0.65

Polyphen

0.10

Vest4

0.027

MutPred

0.22

Loss of glycosylation at S86 (P = 0.2154);

MVP

0.35

MPC

0.32

ClinPred

0.020

GERP RS

2.8

Varity_R

0.086

gMVP

0.095

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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