chr18-79977397-C-T

Position:

• chr18-79977397-C-T

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.257+201G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 544,396 control chromosomes in the GnomAD database, including 178,505 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (42929 hom., cov: 33)
  • Exomes 𝑓: 0.83 (135576 hom.)
• Consequence: TXNL4A NM_006701.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.492

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=-0.91).
• BP6: Variant 18-79977397-C-T is Benign according to our data. Variant chr18-79977397-C-T is described in ClinVar as [Benign]. Clinvar id is 1237111.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXNL4A	NM_006701.5	c.257+201G>A		intron_variant		ENST00000269601.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXNL4A	ENST00000269601.10	c.257+201G>A		intron_variant		1	NM_006701.5	P1

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110964 AN: 152044 Hom.: 42925 Cov.: 33

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.873

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.912

Gnomad SAS AF: 0.883

Gnomad FIN AF: 0.892

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.731

GnomAD4 exome AF: 0.828 AC: 324713 AN: 392234 Hom.: 135576 Cov.: 3 AF XY: 0.831 AC XY: 170881 AN XY: 205720

Gnomad4 AFR exome AF: 0.450

Gnomad4 AMR exome AF: 0.809

Gnomad4 ASJ exome AF: 0.735

Gnomad4 EAS exome AF: 0.878

Gnomad4 SAS exome AF: 0.875

Gnomad4 FIN exome AF: 0.881

Gnomad4 NFE exome AF: 0.833

Gnomad4 OTH exome AF: 0.801

GnomAD4 genome AF: 0.729 AC: 110999 AN: 152162 Hom.: 42929 Cov.: 33 AF XY: 0.739 AC XY: 54938 AN XY: 74386

Gnomad4 AFR AF: 0.449

Gnomad4 AMR AF: 0.808

Gnomad4 ASJ AF: 0.726

Gnomad4 EAS AF: 0.912

Gnomad4 SAS AF: 0.882

Gnomad4 FIN AF: 0.892

Gnomad4 NFE AF: 0.831

Gnomad4 OTH AF: 0.734

Alfa AF: 0.787 Hom.: 16933

Bravo AF: 0.707

Asia WGS AF: 0.867 AC: 3015 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.57
DANN	Benign	0.62

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

Other links and lift over

dbSNP: rs11081576; hg19: chr18-77737397;