Genetic Variant TXLNG:p.Ile246Val (chrX-16829642-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.07

Publications

8 publications found

Variant links:

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]

TXLNG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXLNG	NM_018360.3 link	c.736A>G	p.Ile246Val	missense_variant	Exon 5 of 10	ENST00000380122.10	NP_060830.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXLNG	ENST00000380122.10 link	c.736A>G	p.Ile246Val	missense_variant	Exon 5 of 10	1	NM_018360.3	ENSP00000369465.5
TXLNG	ENST00000398155.4 link	c.340A>G	p.Ile114Val	missense_variant	Exon 3 of 8	1		ENSP00000381222.4

Frequencies

GnomAD3 genomes

AF:

0.0203

AC:

2277

AN:

112007

Hom.:

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0292

AC XY:

10596

AN XY:

363442

show subpopulations

African (AFR)

AF:

0.00337

AC:

AN:

26400

American (AMR)

AF:

0.00662

AC:

233

AN:

35198

Ashkenazi Jewish (ASJ)

AF:

0.00222

AC:

AN:

19382

East Asian (EAS)

AF:

0.0000331

AC:

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:

AN:

4137

European-Non Finnish (NFE)

AF:

0.0331

AC:

27863

AN:

842018

Other (OTH)

AF:

0.0239

AC:

1102

AN:

46089

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

1225

2450

3675

4900

6125

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1068

2136

3204

4272

5340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0203

AC:

2277

AN:

112061

Hom.:

Cov.:

AF XY:

0.0206

AC XY:

705

AN XY:

34235

show subpopulations

African (AFR)

AF:

0.00395

AC:

122

AN:

30894

American (AMR)

AF:

0.00760

AC:

AN:

10530

Ashkenazi Jewish (ASJ)

AF:

0.00227

AC:

AN:

2649

East Asian (EAS)

AF:

0.00

AC:

AN:

3591

South Asian (SAS)

AF:

0.00562

AC:

AN:

2668

European-Finnish (FIN)

AF:

0.0648

AC:

392

AN:

6046

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.0309

AC:

1647

AN:

53260

Other (OTH)

AF:

0.00988

AC:

AN:

1518

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

157

235

314

392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0251

Hom.:

2242

Bravo

AF:

0.0162

TwinsUK

AF:

0.0343

AC:

127

ALSPAC

AF:

0.0339

AC:

ESP6500AA

AF:

0.00548

AC:

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

BayesDel_noAF

Benign

-0.97

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.028

T;.

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.74

T;T

MetaRNN

Benign

0.0025

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

N;.

PhyloP100

1.1

PrimateAI

Benign

0.42

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

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)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over