chr18-79977810-TTTTTG-T

Position:

• chr18-79977810-TTTTTG-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_006701.5(TXNL4A):​c.154-114_154-110del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 718,454 control chromosomes in the GnomAD database, including 49,320 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.35 (9639 hom., cov: 0)
  • Exomes 𝑓: 0.36 (39681 hom.)
• Consequence: TXNL4A NM_006701.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.732

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 -10 ACMG points.

• BP6: Variant 18-79977810-TTTTTG-T is Benign according to our data. Variant chr18-79977810-TTTTTG-T is described in ClinVar as [Benign]. Clinvar id is 1258632.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXNL4A	NM_006701.5	c.154-114_154-110del		intron_variant		ENST00000269601.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXNL4A	ENST00000269601.10	c.154-114_154-110del		intron_variant		1	NM_006701.5	P1

Frequencies

GnomAD3 genomes AF: 0.349 AC: 52730 AN: 151292 Hom.: 9636 Cov.: 0

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.346

GnomAD4 exome AF: 0.356 AC: 201893 AN: 567046 Hom.: 39681 AF XY: 0.360 AC XY: 108393 AN XY: 301124

Gnomad4 AFR exome AF: 0.256

Gnomad4 AMR exome AF: 0.515

Gnomad4 ASJ exome AF: 0.292

Gnomad4 EAS exome AF: 0.478

Gnomad4 SAS exome AF: 0.474

Gnomad4 FIN exome AF: 0.429

Gnomad4 NFE exome AF: 0.319

Gnomad4 OTH exome AF: 0.352

GnomAD4 genome AF: 0.348 AC: 52752 AN: 151408 Hom.: 9639 Cov.: 0 AF XY: 0.357 AC XY: 26375 AN XY: 73930

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.461

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.473

Gnomad4 SAS AF: 0.501

Gnomad4 FIN AF: 0.449

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.349

Alfa AF: 0.346 Hom.: 1161

Bravo AF: 0.345

Asia WGS AF: 0.516 AC: 1791 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs147014161; hg19: chr18-77737810;