NM_018360.3:c.1578G>A

Variant names:

• chrX-16841757-G-A
• rs200307631
• NM_018360.3:c.1578G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_018360.3(TXLNG):​c.1578G>A​(p.Ser526Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000406 in 1,206,881 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 14 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. Synonymous variant affecting the same amino acid position (i.e. S526S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000089 (0 hom., 2 hem., cov: 23)
  • Exomes 𝑓: 0.000036 (0 hom. 12 hem.)
• Consequence: TXLNG NM_018360.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 2 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP7: Synonymous conserved (PhyloP=-1.01 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXLNG	NM_018360.3	c.1578G>A	p.Ser526Ser	synonymous_variant	Exon 10 of 10	ENST00000380122.10	NP_060830.2
TXLNG	NM_001168683.2	c.1182G>A	p.Ser394Ser	synonymous_variant	Exon 8 of 8		NP_001162154.1
TXLNG	XM_024452400.2	c.1461G>A	p.Ser487Ser	synonymous_variant	Exon 10 of 10		XP_024308168.1
TXLNG	XM_017029631.2	c.963G>A	p.Ser321Ser	synonymous_variant	Exon 7 of 7		XP_016885120.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXLNG	ENST00000380122.10	c.1578G>A	p.Ser526Ser	synonymous_variant	Exon 10 of 10	1	NM_018360.3	ENSP00000369465.5
TXLNG	ENST00000398155.4	c.1182G>A	p.Ser394Ser	synonymous_variant	Exon 8 of 8	1		ENSP00000381222.4
TXLNG	ENST00000485153.1	n.469G>A		non_coding_transcript_exon_variant	Exon 2 of 2	3
RBBP7	ENST00000425696.5	c.*8-2367C>T		intron_variant	Intron 4 of 4	5		ENSP00000415747.1

Frequencies

GnomAD3 genomes AF: 0.0000893 AC: 10 AN: 111943 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00111

Gnomad SAS AF: 0.000736

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000752

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000619 AC: 11 AN: 177779 AF XY: 0.0000635

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000374

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000292

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000503

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000356 AC: 39 AN: 1094885 Hom.: 0 Cov.: 31 AF XY: 0.0000333 AC XY: 12 AN XY: 360609

African (AFR) AF: 0.0000380 AC: 1 AN: 26313

American (AMR) AF: 0.00 AC: 0 AN: 34894

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19120

East Asian (EAS) AF: 0.0000994 AC: 3 AN: 30184

South Asian (SAS) AF: 0.000149 AC: 8 AN: 53539

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40413

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4103

European-Non Finnish (NFE) AF: 0.0000274 AC: 23 AN: 840371

Other (OTH) AF: 0.0000871 AC: 4 AN: 45948

GnomAD4 genome AF: 0.0000893 AC: 10 AN: 111996 Hom.: 0 Cov.: 23 AF XY: 0.0000585 AC XY: 2 AN XY: 34170

African (AFR) AF: 0.00 AC: 0 AN: 30848

American (AMR) AF: 0.00 AC: 0 AN: 10588

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2645

East Asian (EAS) AF: 0.00112 AC: 4 AN: 3587

South Asian (SAS) AF: 0.000738 AC: 2 AN: 2710

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6034

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.0000752 AC: 4 AN: 53160

Other (OTH) AF: 0.00 AC: 0 AN: 1520

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000453

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.018
DANN	Benign	0.80
PhyloP100		-1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs200307631; hg19: chrX-16859880; COSMIC: COSV58112524; COSMIC: COSV58112524;