Genetic Variant NM_018360.3:c.112G>C (chrX-16818583-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_018360.3(TXLNG):c.112G>C(p.Gly38Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000915 in 1,093,028 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G38S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

TXLNG
NM_018360.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.28

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30575106).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXLNG	NM_018360.3 link	c.112G>C	p.Gly38Arg	missense_variant	Exon 2 of 10	ENST00000380122.10	NP_060830.2	Q9NUQ3-1
TXLNG	XM_047442249.1 link	c.112G>C	p.Gly38Arg	missense_variant	Exon 2 of 10		XP_047298205.1
TXLNG	XM_024452400.2 link	c.-6G>C		5_prime_UTR_variant	Exon 2 of 10		XP_024308168.1
TXLNG	NM_001168683.2 link	c.103-9511G>C		intron_variant	Intron 1 of 7		NP_001162154.1	Q9NUQ3-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXLNG	ENST00000380122.10 link	c.112G>C	p.Gly38Arg	missense_variant	Exon 2 of 10	1	NM_018360.3	ENSP00000369465.5		Q9NUQ3-1
TXLNG	ENST00000398155.4 link	c.103-9511G>C		intron_variant	Intron 1 of 7	1		ENSP00000381222.4		Q9NUQ3-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000561

AC:

AN:

178221

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000727

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.15e-7

AC:

AN:

1093028

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

359286

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26273

American (AMR)

AF:

0.00

AC:

AN:

34855

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19196

East Asian (EAS)

AF:

0.0000332

AC:

AN:

30108

South Asian (SAS)

AF:

0.00

AC:

AN:

53481

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40436

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3781

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

839041

Other (OTH)

AF:

0.00

AC:

AN:

45857

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.070

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.80

M_CAP

Benign

0.053

MetaRNN

Benign

0.31

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

2.3

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.48

REVEL

Benign

0.18

Sift

Uncertain

0.014

Sift4G

Uncertain

0.018

Polyphen

0.88

Vest4

0.49

MutPred

0.33

Gain of MoRF binding (P = 0.0204);

MVP

0.28

MPC

0.76

ClinPred

0.57

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.25

gMVP

0.17

Mutation Taster

=71/29

polymorphism

(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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NM_018360.3:c.112G>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over