Variant rs5969783 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

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. 12/21 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.07

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

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. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 31 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TXLNG	NM_018360.3 linkuse as main transcript	c.736A>G	p.Ile246Val	missense_variant	5/10	ENST00000380122.10	NP_060830.2	Q9NUQ3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TXLNG	ENST00000380122.10 linkuse as main transcript	c.736A>G	p.Ile246Val	missense_variant	5/10	1	NM_018360.3	ENSP00000369465.5		Q9NUQ3-1
TXLNG	ENST00000398155.4 linkuse as main transcript	c.340A>G	p.Ile114Val	missense_variant	3/8	1		ENSP00000381222.4		Q9NUQ3-2

Frequencies

GnomAD3 genomes

AF:

0.0203

AC:

2277

AN:

112007

Hom.:

Cov.:

AF XY:

0.0206

AC XY:

704

AN XY:

34171

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

GnomAD3 exomes

AF:

0.0221

AC:

4048

AN:

183042

Hom.:

AF XY:

0.0208

AC XY:

1407

AN XY:

67514

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 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.:

AF XY:

0.0292

AC XY:

10596

AN XY:

363442

show subpopulations

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.:

Cov.:

AF XY:

0.0206

AC XY:

705

AN XY:

34235

show subpopulations

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:

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

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;.

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over