18-79986891-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_006701.5(TXNL4A):c.153+1349A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0198 in 483,418 control chromosomes in the GnomAD database, including 147 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (76 hom., cov: 33)
  • Exomes 𝑓: 0.018 (71 hom.)
• Consequence: TXNL4A NM_006701.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.01

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 18-79986891-T-C is Benign according to our data. Variant chr18-79986891-T-C is described in ClinVar as [Benign]. Clinvar id is 1182672.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0241 (3671/152314) while in subpopulation AFR AF= 0.0478 (1985/41564). AF 95% confidence interval is 0.046. There are 76 homozygotes in gnomad4. There are 1739 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 74 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXNL4A	NM_006701.5	c.153+1349A>G		intron_variant		ENST00000269601.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXNL4A	ENST00000269601.10	c.153+1349A>G		intron_variant		1	NM_006701.5	P1

Frequencies

GnomAD3 genomes AF: 0.0241 AC: 3662 AN: 152196 Hom.: 74 Cov.: 33

Gnomad AFR AF: 0.0478

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0191

Gnomad ASJ AF: 0.0181

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.00217

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0179

Gnomad OTH AF: 0.0306

GnomAD4 exome AF: 0.0178 AC: 5895 AN: 331104 Hom.: 71 AF XY: 0.0179 AC XY: 2795 AN XY: 156476

Gnomad4 AFR exome AF: 0.0509

Gnomad4 AMR exome AF: 0.0191

Gnomad4 ASJ exome AF: 0.0184

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00422

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0175

Gnomad4 OTH exome AF: 0.0178

GnomAD4 genome AF: 0.0241 AC: 3671 AN: 152314 Hom.: 76 Cov.: 33 AF XY: 0.0233 AC XY: 1739 AN XY: 74478

Gnomad4 AFR AF: 0.0478

Gnomad4 AMR AF: 0.0191

Gnomad4 ASJ AF: 0.0181

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00269

Gnomad4 FIN AF: 0.00217

Gnomad4 NFE AF: 0.0179

Gnomad4 OTH AF: 0.0331

Alfa AF: 0.00741 Hom.: 2

Bravo AF: 0.0258

Asia WGS AF: 0.0130 AC: 45 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 19, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.23
Dann	Benign	0.50

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: rs116384147; hg19: chr18-77746891;