chrX-16786536-G-A

Position:

• chrX-16786536-G-A

Variant summary

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

The ENST00000380122.10(TXLNG):​c.49G>A​(p.Glu17Lys) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: TXLNG ENST00000380122.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.13

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=0.25247553).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TXLNG	NM_018360.3	c.49G>A	p.Glu17Lys	missense_variant	1/10	ENST00000380122.10	NP_060830.2
TXLNG	NM_001168683.2	c.49G>A	p.Glu17Lys	missense_variant	1/8		NP_001162154.1
TXLNG	XM_047442249.1	c.49G>A	p.Glu17Lys	missense_variant	1/10		XP_047298205.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TXLNG	ENST00000380122.10	c.49G>A	p.Glu17Lys	missense_variant	1/10	1	NM_018360.3	ENSP00000369465.5
TXLNG	ENST00000398155.4	c.49G>A	p.Glu17Lys	missense_variant	1/8	1		ENSP00000381222.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 988715 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 311029

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: 0.00

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

May 28, 2024

The c.49G>A (p.E17K) alteration is located in exon 1 (coding exon 1) of the TXLNG gene. This alteration results from a G to A substitution at nucleotide position 49, causing the glutamic acid (E) at amino acid position 17 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	0.29
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.064	T;.
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.85	D;D
M_CAP	Pathogenic	0.33	D
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.55	N;N
MutationTaster	Benign	0.89	N;N
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.0	N;N
REVEL	Benign	0.093
Sift	Pathogenic	0.0	D;T
Sift4G	Benign	0.39	T;T
Polyphen		0.97	D;D
Vest4		0.24
MutPred		0.34		Gain of MoRF binding (P = 0.0016);Gain of MoRF binding (P = 0.0016);
MVP		0.47
MPC		0.31
ClinPred		0.63	D
GERP RS		5.2
Varity_R		0.56
gMVP		0.32

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-16804659;