Variant 16-72090641-C-A 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.109G>T(p.Val37Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,818 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

TXNL4B
NM_017853.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.76

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.109G>T	p.Val37Phe	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.109G>T	p.Val37Phe	missense_variant	Exon 2 of 4	1	NM_017853.3	ENSP00000268483.3		Q9NX01
TXNL4B	ENST00000562153.5 link	c.109G>T	p.Val37Phe	missense_variant	Exon 2 of 4	4		ENSP00000454635.2		H3BN11

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251214

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135760

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461818

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 06, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.109G>T (p.V37F) alteration is located in exon 2 (coding exon 1) of the TXNL4B gene. This alteration results from a G to T substitution at nucleotide position 109, causing the valine (V) at amino acid position 37 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

0.24

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Pathogenic

0.16

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

.;T;T;T;T

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.96

D;.;D;.;D

M_CAP

Benign

0.0082

MetaRNN

Uncertain

0.60

D;D;D;D;D

MetaSVM

Benign

-0.61

MutationAssessor

Uncertain

2.3

.;M;M;M;.

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-2.3

N;N;N;N;N

REVEL

Uncertain

0.51

Sift

Benign

0.046

D;T;T;T;D

Sift4G

Uncertain

0.049

.;D;D;D;.

Polyphen

0.89

.;P;P;P;.

Vest4

0.84

MutPred

0.15

Gain of solvent accessibility (P = 0.3602);Gain of solvent accessibility (P = 0.3602);Gain of solvent accessibility (P = 0.3602);Gain of solvent accessibility (P = 0.3602);Gain of solvent accessibility (P = 0.3602);

MVP

0.56

MPC

0.0075

ClinPred

0.80

GERP RS

5.7

Varity_R

0.77

gMVP

0.82

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