chrX-16841675-C-T

Position:

• chrX-16841675-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_018360.3(TXLNG):​c.1496C>T​(p.Ala499Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000826 in 1,209,979 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000036 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.0000055 (0 hom. 2 hem.)
• Consequence: TXLNG NM_018360.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.195

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03511393).
• BP6: Variant X-16841675-C-T is Benign according to our data. Variant chrX-16841675-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3330353.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXLNG	NM_018360.3	c.1496C>T	p.Ala499Val	missense_variant	10/10	ENST00000380122.10
TXLNG	NM_001168683.2	c.1100C>T	p.Ala367Val	missense_variant	8/8
TXLNG	XM_024452400.2	c.1379C>T	p.Ala460Val	missense_variant	10/10
TXLNG	XM_017029631.2	c.881C>T	p.Ala294Val	missense_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXLNG	ENST00000380122.10	c.1496C>T	p.Ala499Val	missense_variant	10/10	1	NM_018360.3	P1
TXLNG	ENST00000398155.4	c.1100C>T	p.Ala367Val	missense_variant	8/8	1
RBBP7	ENST00000425696.5	c.*8-2285G>A		intron_variant		5
TXLNG	ENST00000485153.1	n.387C>T		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.0000358 AC: 4 AN: 111727 Hom.: 0 Cov.: 23 AF XY: 0.0000295 AC XY: 1 AN XY: 33901

Gnomad AFR AF: 0.000130

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000546 AC: 6 AN: 1098252 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 2 AN XY: 363606

Gnomad4 AFR exome AF: 0.0000379

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000247

Gnomad4 NFE exome AF: 0.00000475

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000358 AC: 4 AN: 111727 Hom.: 0 Cov.: 23 AF XY: 0.0000295 AC XY: 1 AN XY: 33901

Gnomad4 AFR AF: 0.000130

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000264

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.0010
DANN	Benign	0.69
DEOGEN2	Benign	0.025	T;.
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.25	T;T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.035	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.46	N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.37	N;N
REVEL	Benign	0.033
Sift	Benign	0.28	T;T
Sift4G	Benign	0.29	T;T
Polyphen		0.0010	B;B
Vest4		0.020
MVP		0.043
MPC		0.0070
ClinPred		0.23	T
GERP RS		-12
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.032
gMVP		0.088

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

Other links and lift over

dbSNP: rs1486780340; hg19: chrX-16859798;