NM_018360.3:c.1527A>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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. 14/20 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, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.131

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:

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 -20 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 VariationId is 714920.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 7 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018360.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXLNG	NM_018360.3	MANE Select	c.1527A>C	p.Arg509Ser	missense	Exon 10 of 10	NP_060830.2	Q9NUQ3-1
	TXLNG	NM_001168683.2		c.1131A>C	p.Arg377Ser	missense	Exon 8 of 8	NP_001162154.1	Q9NUQ3-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TXLNG	ENST00000380122.10	TSL:1 MANE Select	c.1527A>C	p.Arg509Ser	missense	Exon 10 of 10	ENSP00000369465.5	Q9NUQ3-1
TXLNG	ENST00000398155.4	TSL:1	c.1131A>C	p.Arg377Ser	missense	Exon 8 of 8	ENSP00000381222.4	Q9NUQ3-2
TXLNG	ENST00000919097.1		c.1512A>C	p.Arg504Ser	missense	Exon 10 of 10	ENSP00000589156.1

Frequencies

GnomAD3 genomes

AF:

0.00856

AC:

958

AN:

111918

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.00271

AC:

496

AN:

183038

AF XY:

0.00154

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 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

African (AFR)

AF:

0.0321

AC:

848

AN:

26402

American (AMR)

AF:

0.00179

AC:

AN:

35199

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19379

East Asian (EAS)

AF:

0.00

AC:

AN:

30206

South Asian (SAS)

AF:

0.0000739

AC:

AN:

54136

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40533

Middle Eastern (MID)

AF:

0.00121

AC:

AN:

4134

European-Non Finnish (NFE)

AF:

0.0000142

AC:

AN:

842127

Other (OTH)

AF:

0.00193

AC:

AN:

46094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

135

180

225

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00857

AC:

960

AN:

111971

Hom.:

Cov.:

AF XY:

0.00746

AC XY:

255

AN XY:

34171

show subpopulations

African (AFR)

AF:

0.0296

AC:

911

AN:

30797

American (AMR)

AF:

0.00311

AC:

AN:

10601

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2646

East Asian (EAS)

AF:

0.00

AC:

AN:

3584

South Asian (SAS)

AF:

0.00

AC:

AN:

2686

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6077

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.0000941

AC:

AN:

53160

Other (OTH)

AF:

0.00726

AC:

AN:

1516

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

101

134

168

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00344

Hom.:

146

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.88

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.96

(source)

DANN

Benign

0.44

DEOGEN2

Benign

0.029

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.49

MetaRNN

Benign

0.0029

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

PhyloP100

-0.13

PrimateAI

Benign

0.24

PROVEAN

Benign

0.63

REVEL

Benign

0.036

Sift

Benign

0.74

Sift4G

Benign

0.67

Polyphen

0.0

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

Mutation Taster

=100/0

polymorphism (auto)

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over