chrX-16820208-A-G

Variant names:

• chrX-16820208-A-G
• rs371041077
• NM_018360.3:c.451A>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_018360.3(TXLNG):​c.451A>G​(p.Thr151Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000029 in 1,208,210 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000045 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.000027 (0 hom. 7 hem.)
• Consequence: TXLNG NM_018360.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.29
• 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2989415).
• BS2: High Hemizygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXLNG	NM_018360.3	c.451A>G	p.Thr151Ala	missense_variant	Exon 3 of 10	ENST00000380122.10	NP_060830.2
TXLNG	XM_024452400.2	c.334A>G	p.Thr112Ala	missense_variant	Exon 3 of 10		XP_024308168.1
TXLNG	XM_047442249.1	c.451A>G	p.Thr151Ala	missense_variant	Exon 3 of 10		XP_047298205.1
TXLNG	NM_001168683.2	c.103-7886A>G		intron_variant	Intron 1 of 7		NP_001162154.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXLNG	ENST00000380122.10	c.451A>G	p.Thr151Ala	missense_variant	Exon 3 of 10	1	NM_018360.3	ENSP00000369465.5
TXLNG	ENST00000398155.4	c.103-7886A>G		intron_variant	Intron 1 of 7	1		ENSP00000381222.4

Frequencies

GnomAD3 genomes AF: 0.0000449 AC: 5 AN: 111254 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000327

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000753

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000387 AC: 7 AN: 181081 AF XY: 0.0000305

Gnomad AFR exome AF: 0.00

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: 0.0000863

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000273 AC: 30 AN: 1096956 Hom.: 0 Cov.: 28 AF XY: 0.0000193 AC XY: 7 AN XY: 362378

African (AFR) AF: 0.0000380 AC: 1 AN: 26341

American (AMR) AF: 0.00 AC: 0 AN: 35073

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19343

East Asian (EAS) AF: 0.00 AC: 0 AN: 30139

South Asian (SAS) AF: 0.00 AC: 0 AN: 53885

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40493

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4131

European-Non Finnish (NFE) AF: 0.0000333 AC: 28 AN: 841502

Other (OTH) AF: 0.0000217 AC: 1 AN: 46049

GnomAD4 genome AF: 0.0000449 AC: 5 AN: 111254 Hom.: 0 Cov.: 23 AF XY: 0.0000299 AC XY: 1 AN XY: 33458

African (AFR) AF: 0.0000327 AC: 1 AN: 30546

American (AMR) AF: 0.00 AC: 0 AN: 10386

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2642

East Asian (EAS) AF: 0.00 AC: 0 AN: 3590

South Asian (SAS) AF: 0.00 AC: 0 AN: 2621

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5947

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.0000753 AC: 4 AN: 53097

Other (OTH) AF: 0.00 AC: 0 AN: 1506

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000529

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000149 AC: 1

ExAC AF: 0.0000659 AC: 8

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.451A>G (p.T151A) alteration is located in exon 3 (coding exon 3) of the TXLNG gene. This alteration results from a A to G substitution at nucleotide position 451, causing the threonine (T) at amino acid position 151 to be replaced by an alanine (A). 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	0.21
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.77	T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		9.3
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.29
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.036	D
Polyphen		0.013	B
Vest4		0.55
MVP		0.47
MPC		0.36
ClinPred		0.28	T
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.65
gMVP		0.30
Mutation Taster		=30/70	disease causing

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: rs371041077; hg19: chrX-16838331;