Genetic Variant TXLNA:p.Leu212Phe (chr1-32187990-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_175852.4(TXLNA):c.634C>T(p.Leu212Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TXLNA
NM_175852.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.38

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16832927).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXLNA	NM_175852.4 link	c.634C>T	p.Leu212Phe	missense_variant	Exon 5 of 11	ENST00000373610.8	NP_787048.1	P40222

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXLNA	ENST00000373610.8 link	c.634C>T	p.Leu212Phe	missense_variant	Exon 5 of 11	1	NM_175852.4	ENSP00000362712.3		P40222
TXLNA	ENST00000373609.1 link	c.634C>T	p.Leu212Phe	missense_variant	Exon 4 of 10	1		ENSP00000362711.1		P40222

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461566

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727024

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86164

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111878

Other (OTH)

AF:

0.00

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00000573

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 03, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.634C>T (p.L212F) alteration is located in exon 5 (coding exon 4) of the TXLNA gene. This alteration results from a C to T substitution at nucleotide position 634, causing the leucine (L) at amino acid position 212 to be replaced by a phenylalanine (F). 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

0.12

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;T

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.061

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.58

.;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.57

N;N

PhyloP100

2.4

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.088

Sift

Benign

0.27

T;T

Sift4G

Benign

0.61

T;T

Polyphen

0.91

P;P

Vest4

0.25

MutPred

0.44

Gain of helix (P = 0.0496);Gain of helix (P = 0.0496);

MVP

0.093

MPC

0.88

ClinPred

0.52

GERP RS

1.8

Varity_R

0.044

gMVP

0.048

Mutation Taster

=88/12

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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1-32187990-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over