Variant 16-72090670-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_017853.3(TXNL4B):c.80T>C(p.Val27Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000502 in 1,614,098 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

TXNL4B
NM_017853.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.07

Variant links:

Genes affected

TXNL4B (HGNC:26041): (thioredoxin like 4B) Predicted to be involved in mRNA splicing, via spliceosome. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TXNL4B links:

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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 rank	MANE	Protein	UniProt
TXNL4B	NM_017853.3 link	c.80T>C	p.Val27Ala	missense_variant	Exon 2 of 4	ENST00000268483.8	NP_060323.1	Q9NX01

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXNL4B	ENST00000268483.8 link	c.80T>C	p.Val27Ala	missense_variant	Exon 2 of 4	1	NM_017853.3	ENSP00000268483.3		Q9NX01
TXNL4B	ENST00000562153.5 link	c.80T>C	p.Val27Ala	missense_variant	Exon 2 of 4	4		ENSP00000454635.2		H3BN11

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000868

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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

GnomAD3 exomes

AF:

0.0000875

AC:

AN:

251342

Hom.:

AF XY:

0.0000957

AC XY:

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.00129

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:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000294

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00116

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:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.000250

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.000868

Gnomad4 AMR

AF:

0.000131

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:

0.000200

Hom.:

Bravo

AF:

0.000412

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.80T>C (p.V27A) alteration is located in exon 2 (coding exon 1) of the TXNL4B gene. This alteration results from a T to C substitution at nucleotide position 80, causing the valine (V) at amino acid position 27 to be replaced by an alanine (A). 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

0.81

BayesDel_addAF

Uncertain

0.041

BayesDel_noAF

Pathogenic

0.25

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.44

.;T;T;T;T

Eigen

Pathogenic

0.91

Eigen_PC

Pathogenic

0.87

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;.;D;.;D

M_CAP

Benign

0.045

MetaRNN

Uncertain

0.62

D;D;D;D;D

MetaSVM

Uncertain

0.033

MutationAssessor

Pathogenic

3.3

.;M;M;M;.

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-3.7

D;D;D;D;D

REVEL

Pathogenic

0.86

Sift

Uncertain

0.0010

D;D;D;D;D

Sift4G

Uncertain

0.0030

.;D;D;D;.

Polyphen

1.0

.;D;D;D;.

Vest4

0.88

MVP

0.25

MPC

0.017

ClinPred

0.55

GERP RS

5.7

Varity_R

0.73

gMVP

0.79

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