X-16832668-G-T

Variant names:

• chrX-16832668-G-T
• rs769513453
• NM_018360.3:c.910G>T

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.910G>T​(p.Val304Leu) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V304M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 24)
• Consequence: TXLNG NM_018360.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.40
• Publications: 0 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=0.20055088).

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.910G>T	p.Val304Leu	missense	Exon 6 of 10	NP_060830.2	Q9NUQ3-1
	TXLNG	NM_001168683.2		c.514G>T	p.Val172Leu	missense	Exon 4 of 8	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.910G>T	p.Val304Leu	missense	Exon 6 of 10	ENSP00000369465.5	Q9NUQ3-1
	TXLNG	ENST00000398155.4	TSL:1	c.514G>T	p.Val172Leu	missense	Exon 4 of 8	ENSP00000381222.4	Q9NUQ3-2
	TXLNG	ENST00000919097.1		c.895G>T	p.Val299Leu	missense	Exon 6 of 10	ENSP00000589156.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 24

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	Uncertain	0.56
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.020	N
PhyloP100		2.4
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.15
Sift	Benign	0.20	T
Sift4G	Benign	0.32	T
Polyphen		0.012	B
Vest4		0.20
MutPred		0.51		Loss of MoRF binding (P = 0.1701)
MVP		0.33
MPC		0.31
ClinPred		0.80	D
GERP RS		5.3
Varity_R		0.41
gMVP		0.44
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs769513453; hg19: chrX-16850791;