X-16841756-C-T

Position:

chrX-16841756-C-T

Variant summary

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

The NM_018360.3(TXLNG):c.1577C>T(p.Ser526Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000123 in 1,207,059 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 44 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.

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., 11 hem., cov: 23)

Exomes 𝑓: 0.000090 ( 0 hom. 33 hem. )

Consequence

TXLNG
NM_018360.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.57

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:

TXLNG (HGNC:):

TXLNG 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=0.010855734).

BS2

High Hemizygotes in GnomAd4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TXLNG	NM_018360.3 linkuse as main transcript	c.1577C>T	p.Ser526Leu	missense_variant	10/10	ENST00000380122.10	NP_060830.2	Q9NUQ3-1
TXLNG	NM_001168683.2 linkuse as main transcript	c.1181C>T	p.Ser394Leu	missense_variant	8/8		NP_001162154.1	Q9NUQ3-2
TXLNG	XM_024452400.2 linkuse as main transcript	c.1460C>T	p.Ser487Leu	missense_variant	10/10		XP_024308168.1
TXLNG	XM_017029631.2 linkuse as main transcript	c.962C>T	p.Ser321Leu	missense_variant	7/7		XP_016885120.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TXLNG	ENST00000380122.10 linkuse as main transcript	c.1577C>T	p.Ser526Leu	missense_variant	10/10	1	NM_018360.3	ENSP00000369465.5	Q9NUQ3-1
TXLNG	ENST00000398155.4 linkuse as main transcript	c.1181C>T	p.Ser394Leu	missense_variant	8/8	1		ENSP00000381222.4	Q9NUQ3-2
RBBP7	ENST00000425696.5 linkuse as main transcript	c.*8-2366G>A		intron_variant		5		ENSP00000415747.1	Q5JNZ6
TXLNG	ENST00000485153.1 linkuse as main transcript	n.468C>T		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.000447

AC:

AN:

111871

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

34039

show subpopulations

Gnomad AFR

AF:

0.00143

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000753

Gnomad OTH

AF:

0.00134

GnomAD3 exomes

AF:

0.000208

AC:

AN:

178164

Hom.:

AF XY:

0.000253

AC XY:

AN XY:

63322

show subpopulations

Gnomad AFR exome

AF:

0.00168

Gnomad AMR exome

AF:

0.0000747

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.000280

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000628

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000904

AC:

AN:

1095137

Hom.:

Cov.:

AF XY:

0.0000915

AC XY:

AN XY:

360815

show subpopulations

Gnomad4 AFR exome

AF:

0.00198

Gnomad4 AMR exome

AF:

0.0000860

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000299

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000226

Gnomad4 OTH exome

AF:

0.000196

GnomAD4 genome

AF:

0.000447

AC:

AN:

111922

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

34100

show subpopulations

Gnomad4 AFR

AF:

0.00143

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000753

Gnomad4 OTH

AF:

0.00132

Alfa

AF:

0.000122

Hom.:

Bravo

AF:

0.000589

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00261

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.000305

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 24, 2024

The c.1577C>T (p.S526L) alteration is located in exon 10 (coding exon 10) of the TXLNG gene. This alteration results from a C to T substitution at nucleotide position 1577, causing the serine (S) at amino acid position 526 to be replaced by a leucine (L). 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

0.14

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.067

T;.

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.71

T;T

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

M;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.057

Sift

Uncertain

0.0040

D;D

Sift4G

Benign

0.44

T;T

Polyphen

0.12

B;B

Vest4

0.027

MVP

0.10

MPC

0.015

ClinPred

0.026

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.14

gMVP

0.23

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