rs1169938690
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_031372.4(HNRNPDL):āc.332A>Cā(p.His111Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H111Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_031372.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HNRNPDL | NM_031372.4 | c.332A>C | p.His111Pro | missense_variant | 1/8 | ENST00000295470.10 | |
HNRNPDL | NM_001207000.1 | c.332A>C | p.His111Pro | missense_variant | 1/7 | ||
HNRNPDL | NR_003249.2 | n.867A>C | non_coding_transcript_exon_variant | 1/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HNRNPDL | ENST00000295470.10 | c.332A>C | p.His111Pro | missense_variant | 1/8 | 1 | NM_031372.4 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461262Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 726978
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Autosomal dominant limb-girdle muscular dystrophy type 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 01, 2023 | This sequence change replaces histidine, which is basic and polar, with proline, which is neutral and non-polar, at codon 111 of the HNRNPDL protein (p.His111Pro). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with HNRNPDL-related conditions. ClinVar contains an entry for this variant (Variation ID: 533017). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The proline amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at