chr18-79986403-T-A

Position:

• chr18-79986403-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006701.5(TXNL4A):​c.153+1837A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 151,974 control chromosomes in the GnomAD database, including 6,856 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.28 (6856 hom., cov: 32)
• Consequence: TXNL4A NM_006701.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.344

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=-0.8).
• BP6: Variant 18-79986403-T-A is Benign according to our data. Variant chr18-79986403-T-A is described in ClinVar as [Benign]. Clinvar id is 1259977.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXNL4A	NM_006701.5	c.153+1837A>T		intron_variant		ENST00000269601.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXNL4A	ENST00000269601.10	c.153+1837A>T		intron_variant		1	NM_006701.5	P1

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42226 AN: 151856 Hom.: 6856 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.276

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.278 AC: 42229 AN: 151974 Hom.: 6856 Cov.: 32 AF XY: 0.276 AC XY: 20507 AN XY: 74272

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.277

Alfa AF: 0.317 Hom.: 1010

Bravo AF: 0.264

Asia WGS AF: 0.146 AC: 508 AN: 3476

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.7
DANN	Benign	0.70

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: rs11663328; hg19: chr18-77746403;