4-82426133-T-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_031372.4(HNRNPDL):c.1193-4A>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Consequence
HNRNPDL
NM_031372.4 splice_region, splice_polypyrimidine_tract, intron
NM_031372.4 splice_region, splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.9898
2
Clinical Significance
Conservation
PhyloP100: 0.775
Genes affected
HNRNPDL (HGNC:5037): (heterogeneous nuclear ribonucleoprotein D like) This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA binding proteins and they complex with heterogeneous nuclear RNA (hnRNA). These proteins are associated with pre-mRNAs in the nucleus and appear to influence pre-mRNA processing and other aspects of mRNA metabolism and transport. While all of the hnRNPs are present in the nucleus, some seem to shuttle between the nucleus and the cytoplasm. The hnRNP proteins have distinct nucleic acid binding properties. The protein encoded by this gene has two RRM domains that bind to RNAs. Three alternatively spliced transcript variants have been described for this gene. One of the variants is probably not translated because the transcript is a candidate for nonsense-mediated mRNA decay. The protein isoforms encoded by this gene are similar to its family member HNRPD. [provided by RefSeq, May 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HNRNPDL | NM_031372.4 | c.1193-4A>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000295470.10 | NP_112740.1 | |||
HNRNPDL | NM_001207000.1 | c.1022-4A>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | NP_001193929.1 | ||||
HNRNPDL | NR_003249.2 | n.1728-4A>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HNRNPDL | ENST00000295470.10 | c.1193-4A>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_031372.4 | ENSP00000295470 | P4 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 29
GnomAD4 exome
Cov.:
29
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal dominant limb-girdle muscular dystrophy type 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 19, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 646823). This variant has not been reported in the literature in individuals affected with HNRNPDL-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 6 of the HNRNPDL gene. It does not directly change the encoded amino acid sequence of the HNRNPDL protein. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: -1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at