rs5969783

chrX-16829642-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_018360.3(TXLNG):c.736A>G(p.Ile246Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0288 in 1,210,143 control chromosomes in the GnomAD database, including 460 homozygotes. There are 11,301 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.020 (31 hom., 705 hem., cov: 23)
  • Exomes 𝑓: 0.030 (429 hom. 10596 hem.)
• Consequence: TXLNG NM_018360.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024654567).
• BP6: Variant X-16829642-A-G is Benign according to our data. Variant chrX-16829642-A-G is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0203 (2277/112061) while in subpopulation NFE AF= 0.0309 (1647/53260). AF 95% confidence interval is 0.0297. There are 31 homozygotes in gnomad4. There are 705 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 31 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXLNG	NM_018360.3	c.736A>G	p.Ile246Val	missense_variant	5/10	ENST00000380122.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXLNG	ENST00000380122.10	c.736A>G	p.Ile246Val	missense_variant	5/10	1	NM_018360.3	P1
TXLNG	ENST00000398155.4	c.340A>G	p.Ile114Val	missense_variant	3/8	1

Frequencies

GnomAD3 genomes AF: 0.0203 AC: 2277 AN: 112007 Hom.: 31 Cov.: 23 AF XY: 0.0206 AC XY: 704 AN XY: 34171

Gnomad AFR AF: 0.00396

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00761

Gnomad ASJ AF: 0.00227

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00561

Gnomad FIN AF: 0.0648

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0309

Gnomad OTH AF: 0.0100

GnomAD3 exomes AF: 0.0221 AC: 4048 AN: 183042 Hom.: 74 AF XY: 0.0208 AC XY: 1407 AN XY: 67514

Gnomad AFR exome AF: 0.00380

Gnomad AMR exome AF: 0.00577

Gnomad ASJ exome AF: 0.00227

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00714

Gnomad FIN exome AF: 0.0726

Gnomad NFE exome AF: 0.0297

Gnomad OTH exome AF: 0.0219

GnomAD4 exome AF: 0.0297 AC: 32630 AN: 1098082 Hom.: 429 Cov.: 30 AF XY: 0.0292 AC XY: 10596 AN XY: 363442

Gnomad4 AFR exome AF: 0.00337

Gnomad4 AMR exome AF: 0.00662

Gnomad4 ASJ exome AF: 0.00222

Gnomad4 EAS exome AF: 0.0000331

Gnomad4 SAS exome AF: 0.00696

Gnomad4 FIN exome AF: 0.0716

Gnomad4 NFE exome AF: 0.0331

Gnomad4 OTH exome AF: 0.0239

GnomAD4 genome AF: 0.0203 AC: 2277 AN: 112061 Hom.: 31 Cov.: 23 AF XY: 0.0206 AC XY: 705 AN XY: 34235

Gnomad4 AFR AF: 0.00395

Gnomad4 AMR AF: 0.00760

Gnomad4 ASJ AF: 0.00227

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00562

Gnomad4 FIN AF: 0.0648

Gnomad4 NFE AF: 0.0309

Gnomad4 OTH AF: 0.00988

Alfa AF: 0.0268 Hom.: 1995

Bravo AF: 0.0162

TwinsUK AF: 0.0343 AC: 127

ALSPAC AF: 0.0339 AC: 98

ESP6500AA AF: 0.00548 AC: 21

ESP6500EA AF: 0.0287 AC: 193

ExAC AF: 0.0224 AC: 2716

EpiCase AF: 0.0271

EpiControl AF: 0.0245

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.97
Cadd	Benign	16
Dann	Benign	0.90
DEOGEN2	Benign	0.028	T;.
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.74	T;T
MetaRNN	Benign	0.0025	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N;.
MutationTaster	Benign	0.74	D;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.35	N;N
REVEL	Benign	0.037
Sift	Benign	0.54	T;T
Sift4G	Benign	0.33	T;T
Polyphen		0.0030	B;B
Vest4		0.037
MPC		0.23
ClinPred		0.0032	T
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.081
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.43		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.43		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs5969783; hg19: chrX-16847765;