X-16818861-C-A

Position:

• chrX-16818861-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000380122.10(TXLNG):​c.390C>A​(p.Asn130Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000184 in 1,085,522 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. 12/20 in silico tools predict 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 ENST00000380122.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.40

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08281663).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TXLNG	NM_018360.3	c.390C>A	p.Asn130Lys	missense_variant	2/10	ENST00000380122.10	NP_060830.2
TXLNG	XM_024452400.2	c.273C>A	p.Asn91Lys	missense_variant	2/10		XP_024308168.1
TXLNG	XM_047442249.1	c.390C>A	p.Asn130Lys	missense_variant	2/10		XP_047298205.1
TXLNG	NM_001168683.2	c.103-9233C>A		intron_variant			NP_001162154.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TXLNG	ENST00000380122.10	c.390C>A	p.Asn130Lys	missense_variant	2/10	1	NM_018360.3	ENSP00000369465.5
TXLNG	ENST00000398155.4	c.103-9233C>A		intron_variant		1		ENSP00000381222.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000184 AC: 2 AN: 1085522 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 355030

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000617

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 05, 2022

The c.390C>A (p.N130K) alteration is located in exon 2 (coding exon 2) of the TXLNG gene. This alteration results from a C to A substitution at nucleotide position 390, causing the asparagine (N) at amino acid position 130 to be replaced by a lysine (K). 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	0.10
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	21
DANN	Benign	0.54
DEOGEN2	Benign	0.023	T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
MutationTaster	Benign	1.0	D;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	1.6	N
REVEL	Benign	0.11
Sift	Benign	0.89	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.26
MutPred		0.33		Gain of ubiquitination at N130 (P = 0.0162);
MVP		0.33
MPC		0.32
ClinPred		0.54	D
GERP RS		5.0
Varity_R		0.18
gMVP		0.079

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

Other links and lift over

dbSNP: rs1291665896; hg19: chrX-16836984;