Genetic Variant TXNL4A:c.-60-10880_-60-10879insCTAGCGCGCGCGCATGCCGTCAGCACGCACGGCGCTAGCGCGCGCGCATGCCGTCAGCACGCACGGCG (chr18-79988580-A-ACGCCGTGCGTGCTGACGGCATGCGCGCGCGCTAGCGCCGTGCGTGCTGACGGCATGCGCGCGCGCTAG) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The ENST00000585474.5(TXNL4A):c.-60-10880_-60-10879insCTAGCGCGCGCGCATGCCGTCAGCACGCACGGCGCTAGCGCGCGCGCATGCCGTCAGCACGCACGGCG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000136 in 516,280 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

TXNL4A
ENST00000585474.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.119

Publications

0 publications found

Variant links:

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]

TXNL4A Gene-Disease associations (from GenCC):

choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome
Inheritance: AR, Unknown Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, G2P

TXNL4A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000396 (60/151696) while in subpopulation AFR AF = 0.00136 (56/41252). AF 95% confidence interval is 0.00107. There are 0 homozygotes in GnomAd4. There are 29 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXNL4A	NM_006701.5 link	c.-189_-188insCTAGCGCGCGCGCATGCCGTCAGCACGCACGGCGCTAGCGCGCGCGCATGCCGTCAGCACGCACGGCG		upstream_gene_variant		ENST00000269601.10	NP_006692.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXNL4A	ENST00000269601.10 link	c.-189_-188insCTAGCGCGCGCGCATGCCGTCAGCACGCACGGCGCTAGCGCGCGCGCATGCCGTCAGCACGCACGGCG		upstream_gene_variant		1	NM_006701.5	ENSP00000269601.4

Frequencies

GnomAD3 genomes

AF:

0.000396

AC:

AN:

151588

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00136

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000418

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000480

GnomAD4 exome

AF:

0.0000274

AC:

AN:

364584

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

181738

show subpopulations

African (AFR)

AF:

0.000835

AC:

AN:

8386

American (AMR)

AF:

0.00

AC:

AN:

6496

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8756

East Asian (EAS)

AF:

0.00

AC:

AN:

20546

South Asian (SAS)

AF:

0.00

AC:

AN:

7860

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20538

Middle Eastern (MID)

AF:

0.000698

AC:

AN:

1432

European-Non Finnish (NFE)

AF:

0.00000369

AC:

AN:

271330

Other (OTH)

AF:

0.0000520

AC:

AN:

19240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.700

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000396

AC:

AN:

151696

Hom.:

Cov.:

AF XY:

0.000391

AC XY:

AN XY:

74186

show subpopulations

African (AFR)

AF:

0.00136

AC:

AN:

41252

American (AMR)

AF:

0.0000655

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5104

South Asian (SAS)

AF:

0.000418

AC:

AN:

4786

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67922

Other (OTH)

AF:

0.000475

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.580

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.12

Splicing

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

Publications

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18-79988580-ACGCCGTGCGTGCTGACGGCATGCGCGCGCGCTAG-ACGCCGTGCGTGCTGACGGCATGCGCGCGCGCTAGCGCCGTGCGTGCTGACGGCATGCGCGCGCGCTAGCGCCGTGCGTGCTGACGGCATGCGCGCGCGCTAG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over