18-79988525-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006701.5(TXNL4A):c.-133T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.826 in 1,002,494 control chromosomes in the GnomAD database, including 343,538 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.79 (47575 hom., cov: 33)
  • Exomes 𝑓: 0.83 (295963 hom.)
• Consequence: TXNL4A NM_006701.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.603

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 18-79988525-A-C is Benign according to our data. Variant chr18-79988525-A-C is described in ClinVar as [Benign]. Clinvar id is 1270135.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXNL4A	NM_006701.5	c.-133T>G		5_prime_UTR_variant	1/3	ENST00000269601.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXNL4A	ENST00000269601.10	c.-133T>G		5_prime_UTR_variant	1/3	1	NM_006701.5	P1

Frequencies

GnomAD3 genomes AF: 0.786 AC: 119243 AN: 151780 Hom.: 47552 Cov.: 33

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.828

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.915

Gnomad SAS AF: 0.884

Gnomad FIN AF: 0.892

Gnomad MID AF: 0.761

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.779

GnomAD4 exome AF: 0.833 AC: 708496 AN: 850604 Hom.: 295963 Cov.: 11 AF XY: 0.834 AC XY: 341347 AN XY: 409448

Gnomad4 AFR exome AF: 0.631

Gnomad4 AMR exome AF: 0.823

Gnomad4 ASJ exome AF: 0.733

Gnomad4 EAS exome AF: 0.875

Gnomad4 SAS exome AF: 0.872

Gnomad4 FIN exome AF: 0.878

Gnomad4 NFE exome AF: 0.837

Gnomad4 OTH exome AF: 0.821

GnomAD4 genome AF: 0.786 AC: 119315 AN: 151890 Hom.: 47575 Cov.: 33 AF XY: 0.792 AC XY: 58780 AN XY: 74260

Gnomad4 AFR AF: 0.643

Gnomad4 AMR AF: 0.827

Gnomad4 ASJ AF: 0.727

Gnomad4 EAS AF: 0.915

Gnomad4 SAS AF: 0.883

Gnomad4 FIN AF: 0.892

Gnomad4 NFE AF: 0.832

Gnomad4 OTH AF: 0.782

Alfa AF: 0.811 Hom.: 12285

Bravo AF: 0.771

Asia WGS AF: 0.882 AC: 3054 AN: 3466

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 19, 2021

- -

TXNL4A-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 09, 2023

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	-0.90
Cadd	Benign	8.1
Dann	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

Other links and lift over

dbSNP: rs1077511; hg19: chr18-77748525;