X-16837609-A-G

Variant names:

• chrX-16837609-A-G
• rs989737735
• NM_018360.3:c.1076A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_018360.3(TXLNG):​c.1076A>G​(p.Asp359Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000582 in 1,203,327 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., 2 hem., cov: 23)
  • Exomes 𝑓: 0.0000037 (0 hom. 1 hem.)
• Consequence: TXLNG NM_018360.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.32
• 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]

LOC124905251 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• 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.1076A>G	p.Asp359Gly	missense_variant	Exon 8 of 10	ENST00000380122.10	NP_060830.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXLNG	ENST00000380122.10	c.1076A>G	p.Asp359Gly	missense_variant	Exon 8 of 10	1	NM_018360.3	ENSP00000369465.5
TXLNG	ENST00000398155.4	c.680A>G	p.Asp227Gly	missense_variant	Exon 6 of 8	1		ENSP00000381222.4

Frequencies

GnomAD3 genomes AF: 0.0000267 AC: 3 AN: 112535 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000969

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000566 AC: 1 AN: 176691 AF XY: 0.0000162

Gnomad AFR exome AF: 0.0000776

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000367 AC: 4 AN: 1090792 Hom.: 0 Cov.: 26 AF XY: 0.00000280 AC XY: 1 AN XY: 356628

African (AFR) AF: 0.0000382 AC: 1 AN: 26205

American (AMR) AF: 0.00 AC: 0 AN: 34692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19225

East Asian (EAS) AF: 0.00 AC: 0 AN: 30081

South Asian (SAS) AF: 0.00 AC: 0 AN: 52878

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40437

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4107

European-Non Finnish (NFE) AF: 0.00000239 AC: 2 AN: 837349

Other (OTH) AF: 0.0000218 AC: 1 AN: 45818

GnomAD4 genome AF: 0.0000267 AC: 3 AN: 112535 Hom.: 0 Cov.: 23 AF XY: 0.0000577 AC XY: 2 AN XY: 34677

African (AFR) AF: 0.0000969 AC: 3 AN: 30955

American (AMR) AF: 0.00 AC: 0 AN: 10639

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2655

East Asian (EAS) AF: 0.00 AC: 0 AN: 3625

South Asian (SAS) AF: 0.00 AC: 0 AN: 2754

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6122

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53338

Other (OTH) AF: 0.00 AC: 0 AN: 1521

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 07, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1076A>G (p.D359G) alteration is located in exon 8 (coding exon 8) of the TXLNG gene. This alteration results from a A to G substitution at nucleotide position 1076, causing the aspartic acid (D) at amino acid position 359 to be replaced by a glycine (G). 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	Pathogenic	0.67
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	30
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T;.
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.75	T;T
M_CAP	Pathogenic	0.34	D
MetaRNN	Uncertain	0.59	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M;.
PhyloP100		9.3
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.9	N;N
REVEL	Uncertain	0.29
Sift	Benign	0.20	T;T
Sift4G	Benign	0.23	T;T
Polyphen		0.99	D;D
Vest4		0.58
MutPred		0.57		Loss of stability (P = 0.0118);.;
MVP		0.55
MPC		3.2
ClinPred		0.45	T
GERP RS		5.5
Varity_R		0.68
gMVP		0.62
Mutation Taster		=43/57	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs989737735; hg19: chrX-16855732;