Genetic Variant TXLNG:p.Val304Leu (chrX-16832668-G-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_018360.3(TXLNG):c.910G>C(p.Val304Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,096,702 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V304M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.0000027 ( 0 hom. 2 hem. )

Consequence

TXLNG
NM_018360.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.40

Publications

2 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18282676).

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXLNG	NM_018360.3 link	c.910G>C	p.Val304Leu	missense_variant	Exon 6 of 10	ENST00000380122.10	NP_060830.2	Q9NUQ3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXLNG	ENST00000380122.10 link	c.910G>C	p.Val304Leu	missense_variant	Exon 6 of 10	1	NM_018360.3	ENSP00000369465.5		Q9NUQ3-1
TXLNG	ENST00000398155.4 link	c.514G>C	p.Val172Leu	missense_variant	Exon 4 of 8	1		ENSP00000381222.4		Q9NUQ3-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000556

AC:

AN:

179932

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000371

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:

0.00000274

AC:

AN:

1096702

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

362134

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26346

American (AMR)

AF:

0.0000285

AC:

AN:

35053

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19354

East Asian (EAS)

AF:

0.00

AC:

AN:

30089

South Asian (SAS)

AF:

0.00

AC:

AN:

53972

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40253

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4132

European-Non Finnish (NFE)

AF:

0.00000238

AC:

AN:

841462

Other (OTH)

AF:

0.00

AC:

AN:

46041

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

T;.

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.91

D;D

M_CAP

Uncertain

0.26

MetaRNN

Benign

0.18

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.020

N;.

PhyloP100

2.4

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.15

Sift

Benign

0.20

T;T

Sift4G

Benign

0.32

T;T

Polyphen

0.012

B;B

Vest4

0.20

MutPred

0.51

Loss of MoRF binding (P = 0.1701);.;

MVP

0.33

MPC

0.31

ClinPred

0.32

GERP RS

5.3

Varity_R

0.41

gMVP

0.44

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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X-16832668-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over