rs5969783

Variant names:

• chrX-16829642-A-G
• rs5969783
• NM_018360.3:c.736A>G

Your query was ambiguous. Multiple possible variants found:

• chrX-16829642-A-G
• chrX-16829642-A-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. 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. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 8 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.

• 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 the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 31 gene

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.736A>G	p.Ile246Val	missense	Exon 5 of 10	NP_060830.2
	TXLNG	NM_001168683.2		c.340A>G	p.Ile114Val	missense	Exon 3 of 8	NP_001162154.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXLNG	ENST00000380122.10	TSL:1 MANE Select	c.736A>G	p.Ile246Val	missense	Exon 5 of 10	ENSP00000369465.5
	TXLNG	ENST00000398155.4	TSL:1	c.340A>G	p.Ile114Val	missense	Exon 3 of 8	ENSP00000381222.4
	TXLNG	ENST00000919097.1		c.721A>G	p.Ile241Val	missense	Exon 5 of 10	ENSP00000589156.1

Frequencies

GnomAD3 genomes AF: 0.0203 AC: 2277 AN: 112007 Hom.: 31 Cov.: 23

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

GnomAD2 exomes AF: 0.0221 AC: 4048 AN: 183042 AF XY: 0.0208

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 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

African (AFR) AF: 0.00337 AC: 89 AN: 26400

American (AMR) AF: 0.00662 AC: 233 AN: 35198

Ashkenazi Jewish (ASJ) AF: 0.00222 AC: 43 AN: 19382

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30200

South Asian (SAS) AF: 0.00696 AC: 377 AN: 54137

European-Finnish (FIN) AF: 0.0716 AC: 2903 AN: 40521

Middle Eastern (MID) AF: 0.00459 AC: 19 AN: 4137

European-Non Finnish (NFE) AF: 0.0331 AC: 27863 AN: 842018

Other (OTH) AF: 0.0239 AC: 1102 AN: 46089

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

African (AFR) AF: 0.00395 AC: 122 AN: 30894

American (AMR) AF: 0.00760 AC: 80 AN: 10530

Ashkenazi Jewish (ASJ) AF: 0.00227 AC: 6 AN: 2649

East Asian (EAS) AF: 0.00 AC: 0 AN: 3591

South Asian (SAS) AF: 0.00562 AC: 15 AN: 2668

European-Finnish (FIN) AF: 0.0648 AC: 392 AN: 6046

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.0309 AC: 1647 AN: 53260

Other (OTH) AF: 0.00988 AC: 15 AN: 1518

Alfa AF: 0.0251 Hom.: 2242

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 v4.9

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
MetaRNN	Benign	0.0025	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PhyloP100		1.1
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.35	N
REVEL	Benign	0.037
Sift	Benign	0.54	T
Sift4G	Benign	0.33	T
Polyphen		0.0030	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
Mutation Taster		=93/7	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5969783; hg19: chrX-16847765;