X-16841458-C-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_018360.3(TXLNG):c.1279C>G(p.Leu427Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000434 in 1,209,178 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 187 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 ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., 8 hem., cov: 23)

Exomes 𝑓: 0.00046 ( 0 hom. 179 hem. )

Consequence

TXLNG
NM_018360.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.47

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:

RBBP7 (HGNC:9890): (RB binding protein 7, chromatin remodeling factor) This protein is a ubiquitously expressed nuclear protein and belongs to a highly conserved subfamily of WD-repeat proteins. It is found among several proteins that binds directly to retinoblastoma protein, which regulates cell proliferation. The encoded protein is found in many histone deacetylase complexes, including mSin3 co-repressor complex. It is also present in protein complexes involved in chromatin assembly. This protein can interact with BRCA1 tumor-suppressor gene and may have a role in the regulation of cell proliferation and differentiation. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]

RBBP7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06757125).

BS2

High Hemizygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXLNG	NM_018360.3 link	c.1279C>G	p.Leu427Val	missense_variant	Exon 10 of 10	ENST00000380122.10	NP_060830.2	Q9NUQ3-1
TXLNG	NM_001168683.2 link	c.883C>G	p.Leu295Val	missense_variant	Exon 8 of 8		NP_001162154.1	Q9NUQ3-2
TXLNG	XM_024452400.2 link	c.1162C>G	p.Leu388Val	missense_variant	Exon 10 of 10		XP_024308168.1
TXLNG	XM_017029631.2 link	c.664C>G	p.Leu222Val	missense_variant	Exon 7 of 7		XP_016885120.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TXLNG	ENST00000380122.10 link	c.1279C>G	p.Leu427Val	missense_variant	Exon 10 of 10	1	NM_018360.3	ENSP00000369465.5	Q9NUQ3-1
TXLNG	ENST00000398155.4 link	c.883C>G	p.Leu295Val	missense_variant	Exon 8 of 8	1		ENSP00000381222.4	Q9NUQ3-2
RBBP7	ENST00000425696.5 link	c.*8-2068G>C		intron_variant	Intron 4 of 4	5		ENSP00000415747.1	Q5JNZ6
TXLNG	ENST00000485153.1 link	n.170C>G		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.000170

AC:

AN:

111644

Hom.:

Cov.:

AF XY:

0.000237

AC XY:

AN XY:

33826

show subpopulations

Gnomad AFR

AF:

0.0000653

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000952

Gnomad ASJ

AF:

0.000755

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00833

Gnomad NFE

AF:

0.000188

Gnomad OTH

AF:

0.00134

GnomAD3 exomes

AF:

0.000237

AC:

AN:

181596

Hom.:

AF XY:

0.000287

AC XY:

AN XY:

66254

show subpopulations

Gnomad AFR exome

AF:

0.0000763

Gnomad AMR exome

AF:

0.0000369

Gnomad ASJ exome

AF:

0.000547

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000534

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000431

Gnomad OTH exome

AF:

0.000224

GnomAD4 exome

AF:

0.000463

AC:

508

AN:

1097484

Hom.:

Cov.:

AF XY:

0.000493

AC XY:

179

AN XY:

362958

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000570

Gnomad4 ASJ exome

AF:

0.000672

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.000167

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000533

Gnomad4 OTH exome

AF:

0.000630

GnomAD4 genome

AF:

0.000152

AC:

AN:

111694

Hom.:

Cov.:

AF XY:

0.000236

AC XY:

AN XY:

33886

show subpopulations

Gnomad4 AFR

AF:

0.0000651

Gnomad4 AMR

AF:

0.0000951

Gnomad4 ASJ

AF:

0.000755

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000188

Gnomad4 OTH

AF:

0.00132

Alfa

AF:

0.000521

Hom.:

Bravo

AF:

0.000196

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.000222

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000415

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1279C>G (p.L427V) alteration is located in exon 10 (coding exon 10) of the TXLNG gene. This alteration results from a C to G substitution at nucleotide position 1279, causing the leucine (L) at amino acid position 427 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

T;.

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.068

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

M;.

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.089

Sift

Benign

0.060

T;T

Sift4G

Benign

0.13

T;T

Polyphen

0.49

P;B

Vest4

0.064

MVP

0.18

MPC

0.011

ClinPred

0.066

GERP RS

2.3

Varity_R

0.19

gMVP

0.45

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over