18-79988356-G-A
Variant names:
Variant summary
Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_006701.5(TXNL4A):c.37C>T(p.Gln13*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
TXNL4A
NM_006701.5 stop_gained
NM_006701.5 stop_gained
Scores
4
2
Clinical Significance
Conservation
PhyloP100: 8.67
Publications
2 publications found
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 syndromeInheritance: AR, Unknown Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, G2P
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 7 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 6 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 18-79988356-G-A is Pathogenic according to our data. Variant chr18-79988356-G-A is described in ClinVar as Pathogenic. ClinVar VariationId is 162205.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_006701.5. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TXNL4A | NM_006701.5 | MANE Select | c.37C>T | p.Gln13* | stop_gained | Exon 1 of 3 | NP_006692.1 | ||
| TXNL4A | NM_001305557.2 | c.37C>T | p.Gln13* | stop_gained | Exon 1 of 3 | NP_001292486.1 | |||
| TXNL4A | NR_131175.2 | n.208C>T | non_coding_transcript_exon | Exon 1 of 5 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TXNL4A | ENST00000269601.10 | TSL:1 MANE Select | c.37C>T | p.Gln13* | stop_gained | Exon 1 of 3 | ENSP00000269601.4 | ||
| TXNL4A | ENST00000355491.5 | TSL:1 | n.37C>T | non_coding_transcript_exon | Exon 1 of 4 | ENSP00000347678.4 | |||
| TXNL4A | ENST00000585474.5 | TSL:1 | c.-60-10655C>T | intron | N/A | ENSP00000465572.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000142 AC: 2AN: 1406510Hom.: 0 Cov.: 31 AF XY: 0.00000288 AC XY: 2AN XY: 695540 show subpopulations
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
2
AN:
1406510
Hom.:
Cov.:
31
AF XY:
AC XY:
2
AN XY:
695540
show subpopulations
African (AFR)
AF:
AC:
1
AN:
31738
American (AMR)
AF:
AC:
0
AN:
38102
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25070
East Asian (EAS)
AF:
AC:
0
AN:
36376
South Asian (SAS)
AF:
AC:
0
AN:
80166
European-Finnish (FIN)
AF:
AC:
0
AN:
49400
Middle Eastern (MID)
AF:
AC:
0
AN:
5640
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1082042
Other (OTH)
AF:
AC:
0
AN:
57976
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
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>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome Pathogenic:1Other:1
GeneReviews
Significance:not provided
Review Status:no classification provided
Collection Method:literature only
Dec 04, 2014
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
PhyloP100
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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