Variant 1-32192316-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000373610.8(TXLNA):c.969C>G(p.Ile323Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000183 in 1,613,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

TXLNA
ENST00000373610.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.29

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13371754).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TXLNA	NM_175852.4 linkuse as main transcript	c.969C>G	p.Ile323Met	missense_variant	7/11	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.969C>G	p.Ile323Met	missense_variant	7/11	1	NM_175852.4	ENSP00000362712	P1
TXLNA	ENST00000373609.1 linkuse as main transcript	c.969C>G	p.Ile323Met	missense_variant	6/10	1		ENSP00000362711	P1

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000123

AC:

AN:

251412

Hom.:

AF XY:

0.000132

AC XY:

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.000893

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000149

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000187

AC:

274

AN:

1461590

Hom.:

Cov.:

AF XY:

0.000173

AC XY:

126

AN XY:

727076

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00119

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000193

Gnomad4 OTH exome

AF:

0.000298

GnomAD4 genome

AF:

0.000144

AC:

AN:

152336

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000223

Hom.:

Bravo

AF:

0.000121

ExAC

AF:

0.000115

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

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

Oct 18, 2021

The c.969C>G (p.I323M) alteration is located in exon 7 (coding exon 6) of the TXLNA gene. This alteration results from a C to G substitution at nucleotide position 969, causing the isoleucine (I) at amino acid position 323 to be replaced by a methionine (M). 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

Pathogenic

0.62

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

T;T

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.76

.;T

M_CAP

Benign

0.028

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.27

Sift

Uncertain

0.018

D;D

Sift4G

Benign

0.18

T;T

Polyphen

0.98

D;D

Vest4

0.62

MVP

0.19

MPC

1.2

ClinPred

0.19

GERP RS

-3.9

Varity_R

0.24

gMVP

0.30

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

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