rs771120108
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_031372.4(HNRNPDL):c.114A>G(p.Leu38=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000171 in 1,389,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00017 ( 0 hom. )
Consequence
HNRNPDL
NM_031372.4 synonymous
NM_031372.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.101
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 Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
?
Variant 4-82429577-T-C is Benign according to our data. Variant chr4-82429577-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 464380.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.101 with no splicing effect.
BS2
?
High AC in GnomAd at 24 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HNRNPDL | NM_031372.4 | c.114A>G | p.Leu38= | synonymous_variant | 1/8 | ENST00000295470.10 | |
HNRNPDL | NM_001207000.1 | c.114A>G | p.Leu38= | synonymous_variant | 1/7 | ||
HNRNPDL | NR_003249.2 | n.649A>G | non_coding_transcript_exon_variant | 1/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HNRNPDL | ENST00000295470.10 | c.114A>G | p.Leu38= | synonymous_variant | 1/8 | 1 | NM_031372.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000159 AC: 24AN: 151356Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000512 AC: 1AN: 19536Hom.: 0 AF XY: 0.0000998 AC XY: 1AN XY: 10020
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GnomAD4 exome AF: 0.000172 AC: 213AN: 1238238Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 97AN XY: 601588
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GnomAD4 genome ? AF: 0.000159 AC: 24AN: 151356Hom.: 0 Cov.: 32 AF XY: 0.000162 AC XY: 12AN XY: 73904
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
HNRNPDL-related condition Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 07, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Autosomal dominant limb-girdle muscular dystrophy type 1G Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 28, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at