Variant 1-32188039-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000373610.8(TXLNA):c.683G>A(p.Arg228His) variant causes a missense change. The variant allele was found at a frequency of 0.0000162 in 1,609,486 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. R228R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

TXLNA
ENST00000373610.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.96

Variant links:

Genes affected

TXLNA (HGNC:30685): (taxilin alpha) Predicted to enable syntaxin binding activity. Predicted to be involved in exocytosis. Predicted to act upstream of or within B cell activation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TXLNA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TXLNA	NM_175852.4 linkuse as main transcript	c.683G>A	p.Arg228His	missense_variant	5/11	ENST00000373610.8	NP_787048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TXLNA	ENST00000373610.8 linkuse as main transcript	c.683G>A	p.Arg228His	missense_variant	5/11	1	NM_175852.4	ENSP00000362712	P1
TXLNA	ENST00000373609.1 linkuse as main transcript	c.683G>A	p.Arg228His	missense_variant	4/10	1		ENSP00000362711	P1

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000207

AC:

AN:

241112

Hom.:

AF XY:

0.0000307

AC XY:

AN XY:

130264

show subpopulations

Gnomad AFR exome

AF:

0.000133

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000184

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1457264

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

724340

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.0000455

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000469

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000901

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0000483

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:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000145

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 24, 2022

The c.683G>A (p.R228H) alteration is located in exon 5 (coding exon 4) of the TXLNA gene. This alteration results from a G to A substitution at nucleotide position 683, causing the arginine (R) at amino acid position 228 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.28

T;T

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.93

.;D

M_CAP

Benign

0.023

MetaRNN

Uncertain

0.47

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.3

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.46

PROVEAN

Benign

-2.3

N;N

REVEL

Benign

0.22

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.012

D;D

Polyphen

1.0

D;D

Vest4

0.45

MutPred

0.61

Loss of MoRF binding (P = 0.0095);Loss of MoRF binding (P = 0.0095);

MVP

0.19

MPC

1.3

ClinPred

0.88

GERP RS

5.2

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.23

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over