Genetic Variant TXNL4A:c.153+1617A>G (chr18-79986623-T-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001303471.3(TXNL4A):c.15A>G(p.Arg5Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 985,268 control chromosomes in the GnomAD database, including 335,827 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.79 ( 47656 hom., cov: 33)

Exomes 𝑓: 0.83 ( 288171 hom. )

Consequence

TXNL4A
NM_001303471.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.00600

Variant links:

Genes affected

TXNL4A (HGNC:30551): (thioredoxin like 4A) The protein encoded by this gene is a member of the U5 small ribonucleoprotein particle (snRNP), and is involved in pre-mRNA splicing. This protein contains a thioredoxin-like fold and it is expected to interact with multiple proteins. Protein-protein interactions have been observed with the polyglutamine tract-binding protein 1 (PQBP1). Mutations in both the coding region and promoter region of this gene have been associated with Burn-McKeown syndrome, which is a rare disorder characterized by craniofacial dysmorphisms, cardiac defects, hearing loss, and bilateral choanal atresia. A pseudogene of this gene is found on chromosome 2. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2015]

TXNL4A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 18-79986623-T-C is Benign according to our data. Variant chr18-79986623-T-C is described in ClinVar as [Benign]. Clinvar id is 1177803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.006 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXNL4A	NM_006701.5 link	c.153+1617A>G		intron_variant	Intron 1 of 2	ENST00000269601.10	NP_006692.1	P83876

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXNL4A	ENST00000269601.10 link	c.153+1617A>G		intron_variant	Intron 1 of 2	1	NM_006701.5	ENSP00000269601.4		P83876

Frequencies

GnomAD3 genomes

AF:

0.785

AC:

119430

AN:

152054

Hom.:

47630

Cov.:

show subpopulations

Gnomad AFR

AF:

0.643

Gnomad AMI

AF:

0.874

Gnomad AMR

AF:

0.828

Gnomad ASJ

AF:

0.727

Gnomad EAS

AF:

0.913

Gnomad SAS

AF:

0.884

Gnomad FIN

AF:

0.892

Gnomad MID

AF:

0.756

Gnomad NFE

AF:

0.832

Gnomad OTH

AF:

0.777

GnomAD4 exome

AF:

0.831

AC:

692345

AN:

833096

Hom.:

288171

Cov.:

AF XY:

0.832

AC XY:

320179

AN XY:

384708

show subpopulations

Gnomad4 AFR exome

AF:

0.617

Gnomad4 AMR exome

AF:

0.834

Gnomad4 ASJ exome

AF:

0.737

Gnomad4 EAS exome

AF:

0.916

Gnomad4 SAS exome

AF:

0.873

Gnomad4 FIN exome

AF:

0.858

Gnomad4 NFE exome

AF:

0.835

Gnomad4 OTH exome

AF:

0.826

GnomAD4 genome

AF:

0.785

AC:

119508

AN:

152172

Hom.:

47656

Cov.:

AF XY:

0.791

AC XY:

58875

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.643

Gnomad4 AMR

AF:

0.828

Gnomad4 ASJ

AF:

0.727

Gnomad4 EAS

AF:

0.912

Gnomad4 SAS

AF:

0.883

Gnomad4 FIN

AF:

0.892

Gnomad4 NFE

AF:

0.832

Gnomad4 OTH

AF:

0.780

Alfa

AF:

0.808

Hom.:

8152

Bravo

AF:

0.771

Asia WGS

AF:

0.881

AC:

3063

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 13, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

TXNL4A-related disorder

Benign:1

Sep 18, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

6.1

DANN

Benign

0.86

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