rs142675324

Variant names:

• chrX-16832652-A-C
• rs142675324
• NM_018360.3:c.894A>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_018360.3(TXLNG):​c.894A>C​(p.Glu298Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000703 in 1,209,429 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 25 hemizygotes 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: 𝑓 0.000045 (0 hom., 2 hem., cov: 24)
  • Exomes 𝑓: 0.000073 (0 hom. 23 hem.)
• Consequence: TXLNG NM_018360.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.489
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04652497).
• BS2: High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXLNG	NM_018360.3	c.894A>C	p.Glu298Asp	missense_variant	Exon 6 of 10	ENST00000380122.10	NP_060830.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXLNG	ENST00000380122.10	c.894A>C	p.Glu298Asp	missense_variant	Exon 6 of 10	1	NM_018360.3	ENSP00000369465.5
TXLNG	ENST00000398155.4	c.498A>C	p.Glu166Asp	missense_variant	Exon 4 of 8	1		ENSP00000381222.4

Frequencies

GnomAD3 genomes AF: 0.0000446 AC: 5 AN: 112227 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000324

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: 0.0000751

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000221 AC: 4 AN: 180934 AF XY: 0.0000153

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000369

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000370

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000729 AC: 80 AN: 1097202 Hom.: 0 Cov.: 30 AF XY: 0.0000634 AC XY: 23 AN XY: 362586

African (AFR) AF: 0.00 AC: 0 AN: 26364

American (AMR) AF: 0.0000285 AC: 1 AN: 35082

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19364

East Asian (EAS) AF: 0.00 AC: 0 AN: 30146

South Asian (SAS) AF: 0.00 AC: 0 AN: 53968

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4129

European-Non Finnish (NFE) AF: 0.0000879 AC: 74 AN: 841714

Other (OTH) AF: 0.000109 AC: 5 AN: 46065

GnomAD4 genome AF: 0.0000446 AC: 5 AN: 112227 Hom.: 0 Cov.: 24 AF XY: 0.0000582 AC XY: 2 AN XY: 34373

African (AFR) AF: 0.0000324 AC: 1 AN: 30850

American (AMR) AF: 0.00 AC: 0 AN: 10562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2650

East Asian (EAS) AF: 0.00 AC: 0 AN: 3603

South Asian (SAS) AF: 0.00 AC: 0 AN: 2700

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6170

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.0000751 AC: 4 AN: 53256

Other (OTH) AF: 0.00 AC: 0 AN: 1508

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000264

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000346 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000149 AC: 1

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.894A>C (p.E298D) alteration is located in exon 6 (coding exon 6) of the TXLNG gene. This alteration results from a A to C substitution at nucleotide position 894, causing the glutamic acid (E) at amino acid position 298 to be replaced by an aspartic acid (D). 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	-0.35	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.045	T;.
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.047	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.32	N;.
PhyloP100		0.49
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.86	N;N
REVEL	Benign	0.13
Sift	Benign	0.55	T;T
Sift4G	Benign	0.96	T;T
Polyphen		0.065	B;B
Vest4		0.10
MutPred		0.52		Loss of ubiquitination at K297 (P = 0.1113);.;
MVP		0.31
MPC		0.27
ClinPred		0.038	T
GERP RS		1.6
Varity_R		0.33
gMVP		0.33
Mutation Taster		=95/5	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: rs142675324; hg19: chrX-16850775;