chrX-16841526-T-C

Variant names:

• chrX-16841526-T-C
• rs146909764
• NM_018360.3:c.1347T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_018360.3(TXLNG):​c.1347T>C​(p.Asn449Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000207 in 1,209,735 control chromosomes in the GnomAD database, including 1 homozygotes. There are 107 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., 6 hem., cov: 23)
  • Exomes 𝑓: 0.00021 (1 hom. 101 hem.)
• Consequence: TXLNG NM_018360.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.00
• Publications: 0 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant X-16841526-T-C is Benign according to our data. Variant chrX-16841526-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2660069.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXLNG	NM_018360.3	c.1347T>C	p.Asn449Asn	synonymous_variant	Exon 10 of 10	ENST00000380122.10	NP_060830.2
TXLNG	NM_001168683.2	c.951T>C	p.Asn317Asn	synonymous_variant	Exon 8 of 8		NP_001162154.1
TXLNG	XM_024452400.2	c.1230T>C	p.Asn410Asn	synonymous_variant	Exon 10 of 10		XP_024308168.1
TXLNG	XM_017029631.2	c.732T>C	p.Asn244Asn	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.1347T>C	p.Asn449Asn	synonymous_variant	Exon 10 of 10	1	NM_018360.3	ENSP00000369465.5
TXLNG	ENST00000398155.4	c.951T>C	p.Asn317Asn	synonymous_variant	Exon 8 of 8	1		ENSP00000381222.4
TXLNG	ENST00000485153.1	n.238T>C		non_coding_transcript_exon_variant	Exon 2 of 2	3
RBBP7	ENST00000425696.5	c.*8-2136A>G		intron_variant	Intron 4 of 4	5		ENSP00000415747.1

Frequencies

GnomAD3 genomes AF: 0.000170 AC: 19 AN: 111590 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000952

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00112

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000282

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000333 AC: 61 AN: 183443 AF XY: 0.000368

Gnomad AFR exome AF: 0.0000760

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000125

Gnomad NFE exome AF: 0.000611

Gnomad OTH exome AF: 0.000441

GnomAD4 exome AF: 0.000210 AC: 231 AN: 1098145 Hom.: 1 Cov.: 31 AF XY: 0.000278 AC XY: 101 AN XY: 363513

African (AFR) AF: 0.0000379 AC: 1 AN: 26400

American (AMR) AF: 0.00 AC: 0 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.00 AC: 0 AN: 30205

South Asian (SAS) AF: 0.000425 AC: 23 AN: 54144

European-Finnish (FIN) AF: 0.0000740 AC: 3 AN: 40532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.000230 AC: 194 AN: 842041

Other (OTH) AF: 0.000217 AC: 10 AN: 46093

GnomAD4 genome AF: 0.000170 AC: 19 AN: 111590 Hom.: 0 Cov.: 23 AF XY: 0.000178 AC XY: 6 AN XY: 33788

African (AFR) AF: 0.00 AC: 0 AN: 30678

American (AMR) AF: 0.0000952 AC: 1 AN: 10502

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2640

East Asian (EAS) AF: 0.00 AC: 0 AN: 3545

South Asian (SAS) AF: 0.00112 AC: 3 AN: 2674

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6024

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.000282 AC: 15 AN: 53117

Other (OTH) AF: 0.00 AC: 0 AN: 1488

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.000128

EpiCase AF: 0.000109

EpiControl AF: 0.000237

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TXLNG: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.66
DANN	Benign	0.65
PhyloP100		-1.0
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: rs146909764; hg19: chrX-16859649;