Genetic Variant TXLNG:p.Gly38Ser (chrX-16818583-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.112G>A(p.Gly38Ser) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 9.1e-7 ( 0 hom. 1 hem. )

Failed GnomAD Quality Control

Consequence

TXLNG
NM_018360.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.28

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:

Genome browser will be placed here

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=0.079645514).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXLNG	NM_018360.3 link	c.112G>A	p.Gly38Ser	missense_variant	Exon 2 of 10	ENST00000380122.10	NP_060830.2	Q9NUQ3-1
TXLNG	XM_047442249.1 link	c.112G>A	p.Gly38Ser	missense_variant	Exon 2 of 10		XP_047298205.1
TXLNG	XM_024452400.2 link	c.-6G>A		5_prime_UTR_variant	Exon 2 of 10		XP_024308168.1
TXLNG	NM_001168683.2 link	c.103-9511G>A		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.112G>A	p.Gly38Ser	missense_variant	Exon 2 of 10	1	NM_018360.3	ENSP00000369465.5		Q9NUQ3-1
TXLNG	ENST00000398155.4 link	c.103-9511G>A		intron_variant	Intron 1 of 7	1		ENSP00000381222.4		Q9NUQ3-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000112

AC:

AN:

178221

AF XY:

0.0000317

show subpopulations

Gnomad AFR exome

AF:

0.0000764

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:

0.0000125

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

9.15e-7

AC:

AN:

1093028

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

359286

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26273

American (AMR)

AF:

0.00

AC:

AN:

34855

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19196

East Asian (EAS)

AF:

0.00

AC:

AN:

30108

South Asian (SAS)

AF:

0.00

AC:

AN:

53481

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40436

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3781

European-Non Finnish (NFE)

AF:

0.00000119

AC:

AN:

839041

Other (OTH)

AF:

0.00

AC:

AN:

45857

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 18, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.112G>A (p.G38S) alteration is located in exon 2 (coding exon 2) of the TXLNG gene. This alteration results from a G to A substitution at nucleotide position 112, causing the glycine (G) at amino acid position 38 to be replaced by a serine (S). 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

-0.37

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.042

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.70

M_CAP

Benign

0.022

MetaRNN

Benign

0.080

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PhyloP100

2.3

PrimateAI

Uncertain

0.56

PROVEAN

Benign

0.27

REVEL

Benign

0.038

Sift

Uncertain

0.015

Sift4G

Benign

0.26

Polyphen

0.16

Vest4

0.17

MutPred

0.28

Gain of glycosylation at G38 (P = 0.0108);

MVP

0.28

MPC

0.31

ClinPred

0.49

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.14

Mutation Taster

=87/13

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

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