X-16841706-A-C

Position:

chrX-16841706-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_018360.3(TXLNG):c.1527A>C(p.Arg509Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,210,181 control chromosomes in the GnomAD database, including 20 homozygotes. There are 508 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0086 ( 7 hom., 255 hem., cov: 22)

Exomes 𝑓: 0.00093 ( 13 hom. 253 hem. )

Consequence

TXLNG
NM_018360.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.131

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029144883).

BP6

Variant X-16841706-A-C is Benign according to our data. Variant chrX-16841706-A-C is described in ClinVar as [Benign]. Clinvar id is 714920.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00857 (960/111971) while in subpopulation AFR AF= 0.0296 (911/30797). AF 95% confidence interval is 0.028. There are 7 homozygotes in gnomad4. There are 255 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TXLNG	NM_018360.3 linkuse as main transcript	c.1527A>C	p.Arg509Ser	missense_variant	10/10	ENST00000380122.10
TXLNG	NM_001168683.2 linkuse as main transcript	c.1131A>C	p.Arg377Ser	missense_variant	8/8
TXLNG	XM_024452400.2 linkuse as main transcript	c.1410A>C	p.Arg470Ser	missense_variant	10/10
TXLNG	XM_017029631.2 linkuse as main transcript	c.912A>C	p.Arg304Ser	missense_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXLNG	ENST00000380122.10 linkuse as main transcript	c.1527A>C	p.Arg509Ser	missense_variant	10/10	1	NM_018360.3	P1	Q9NUQ3-1
TXLNG	ENST00000398155.4 linkuse as main transcript	c.1131A>C	p.Arg377Ser	missense_variant	8/8	1			Q9NUQ3-2
RBBP7	ENST00000425696.5 linkuse as main transcript	c.*8-2316T>G		intron_variant		5
TXLNG	ENST00000485153.1 linkuse as main transcript	n.418A>C		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.00856

AC:

958

AN:

111918

Hom.:

Cov.:

AF XY:

0.00745

AC XY:

254

AN XY:

34108

show subpopulations

Gnomad AFR

AF:

0.0296

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00312

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:

0.0000940

Gnomad OTH

AF:

0.00735

GnomAD3 exomes

AF:

0.00271

AC:

496

AN:

183038

Hom.:

AF XY:

0.00154

AC XY:

104

AN XY:

67572

show subpopulations

Gnomad AFR exome

AF:

0.0335

Gnomad AMR exome

AF:

0.00153

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000105

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000368

Gnomad OTH exome

AF:

0.00177

GnomAD4 exome

AF:

0.000930

AC:

1021

AN:

1098210

Hom.:

Cov.:

AF XY:

0.000696

AC XY:

253

AN XY:

363568

show subpopulations

Gnomad4 AFR exome

AF:

0.0321

Gnomad4 AMR exome

AF:

0.00179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000739

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000142

Gnomad4 OTH exome

AF:

0.00193

GnomAD4 genome

AF:

0.00857

AC:

960

AN:

111971

Hom.:

Cov.:

AF XY:

0.00746

AC XY:

255

AN XY:

34171

show subpopulations

Gnomad4 AFR

AF:

0.0296

Gnomad4 AMR

AF:

0.00311

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000941

Gnomad4 OTH

AF:

0.00726

Alfa

AF:

0.00151

Hom.:

Bravo

AF:

0.0104

ESP6500AA

AF:

0.0362

AC:

139

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.00292

AC:

355

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.88

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.96

DANN

Benign

0.44

DEOGEN2

Benign

0.029

T;.

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.49

T;T

MetaRNN

Benign

0.0029

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

0.63

N;N

REVEL

Benign

0.036

Sift

Benign

0.74

T;T

Sift4G

Benign

0.67

T;T

Polyphen

0.0

B;B

Vest4

0.084

MutPred

0.20

Gain of phosphorylation at R509 (P = 0.022);.;

MVP

0.068

MPC

0.0068

ClinPred

0.00077

GERP RS

-2.8

Varity_R

0.23

gMVP

0.13

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