rs138029791

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_018360.3(TXLNG):c.1559C>A(p.Ser520Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000233 in 1,209,163 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 89 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000062 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.00025 ( 0 hom. 88 hem. )

Consequence

TXLNG
NM_018360.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.50

Publications

0 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:

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 Gene-Disease associations (from GenCC):

spermatogenic failure, X-linked, 9
Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

RBBP7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.051718265).

BS2

High Hemizygotes in GnomAdExome4 at 88 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXLNG	NM_018360.3 link	c.1559C>A	p.Ser520Tyr	missense_variant	Exon 10 of 10	ENST00000380122.10	NP_060830.2	Q9NUQ3-1
TXLNG	NM_001168683.2 link	c.1163C>A	p.Ser388Tyr	missense_variant	Exon 8 of 8		NP_001162154.1	Q9NUQ3-2
TXLNG	XM_024452400.2 link	c.1442C>A	p.Ser481Tyr	missense_variant	Exon 10 of 10		XP_024308168.1
TXLNG	XM_017029631.2 link	c.944C>A	p.Ser315Tyr	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.1559C>A	p.Ser520Tyr	missense_variant	Exon 10 of 10	1	NM_018360.3	ENSP00000369465.5	Q9NUQ3-1
TXLNG	ENST00000398155.4 link	c.1163C>A	p.Ser388Tyr	missense_variant	Exon 8 of 8	1		ENSP00000381222.4	Q9NUQ3-2
TXLNG	ENST00000485153.1 link	n.450C>A		non_coding_transcript_exon_variant	Exon 2 of 2	3
RBBP7	ENST00000425696.5 link	c.*8-2348G>T		intron_variant	Intron 4 of 4	5		ENSP00000415747.1	Q5JNZ6

Frequencies

GnomAD3 genomes

AF:

0.0000624

AC:

AN:

112217

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000649

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:

0.0000939

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000608

AC:

AN:

180813

AF XY:

0.0000915

show subpopulations

Gnomad AFR exome

AF:

0.000152

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000111

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000251

AC:

275

AN:

1096946

Hom.:

Cov.:

AF XY:

0.000243

AC XY:

AN XY:

362404

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26343

American (AMR)

AF:

0.00

AC:

AN:

34987

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19285

East Asian (EAS)

AF:

0.00

AC:

AN:

30193

South Asian (SAS)

AF:

0.00

AC:

AN:

53912

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40505

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4119

European-Non Finnish (NFE)

AF:

0.000326

AC:

274

AN:

841567

Other (OTH)

AF:

0.0000217

AC:

AN:

46035

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000624

AC:

AN:

112217

Hom.:

Cov.:

AF XY:

0.0000291

AC XY:

AN XY:

34361

show subpopulations

African (AFR)

AF:

0.0000649

AC:

AN:

30824

American (AMR)

AF:

0.00

AC:

AN:

10630

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2649

East Asian (EAS)

AF:

0.00

AC:

AN:

3607

South Asian (SAS)

AF:

0.00

AC:

AN:

2727

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6091

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.0000939

AC:

AN:

53252

Other (OTH)

AF:

0.00

AC:

AN:

1511

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.433

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000356

Hom.:

Bravo

AF:

0.0000869

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000346

AC:

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.000446

AC:

ExAC

AF:

0.0000576

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 23, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1559C>A (p.S520Y) alteration is located in exon 10 (coding exon 10) of the TXLNG gene. This alteration results from a C to A substitution at nucleotide position 1559, causing the serine (S) at amino acid position 520 to be replaced by a tyrosine (Y). 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

0.095

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.17

T;.

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.60

T;T

M_CAP

Benign

0.036

MetaRNN

Benign

0.052

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

M;.

PhyloP100

1.5

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.6

D;N

REVEL

Benign

0.062

Sift

Uncertain

0.010

D;D

Sift4G

Uncertain

0.017

D;D

Polyphen

0.0010

B;B

Vest4

0.11

MVP

0.043

MPC

0.013

ClinPred

0.074

GERP RS

1.0

Varity_R

0.15

gMVP

0.15

Mutation Taster

=95/5

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs138029791

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over