rs1291665896

Variant names:

• chrX-16818861-C-A
• rs1291665896
• NM_018360.3:c.390C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018360.3(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. 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: 23)
  • Exomes 𝑓: 0.0000018 (0 hom. 0 hem.)
• Consequence: TXLNG NM_018360.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.40
• Publications: 1 publications found

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

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=0.08281663).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018360.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXLNG	NM_018360.3	MANE Select	c.390C>A	p.Asn130Lys	missense	Exon 2 of 10	NP_060830.2	Q9NUQ3-1
	TXLNG	NM_001168683.2		c.103-9233C>A		intron	N/A	NP_001162154.1	Q9NUQ3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXLNG	ENST00000380122.10	TSL:1 MANE Select	c.390C>A	p.Asn130Lys	missense	Exon 2 of 10	ENSP00000369465.5	Q9NUQ3-1
	TXLNG	ENST00000398155.4	TSL:1	c.103-9233C>A		intron	N/A	ENSP00000381222.4	Q9NUQ3-2
	TXLNG	ENST00000919097.1		c.390C>A	p.Asn130Lys	missense	Exon 2 of 10	ENSP00000589156.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00000590 AC: 1 AN: 169490 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000414

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25609

American (AMR) AF: 0.0000617 AC: 2 AN: 32412

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18788

East Asian (EAS) AF: 0.00 AC: 0 AN: 30061

South Asian (SAS) AF: 0.00 AC: 0 AN: 52000

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40329

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4052

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 836800

Other (OTH) AF: 0.00 AC: 0 AN: 45471

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000000000366374), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		4.4
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
Mutation Taster		=82/18	polymorphism

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

Other links and lift over

dbSNP: rs1291665896; hg19: chrX-16836984;