chr4-82429438-G-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_031372.4(HNRNPDL):c.253C>T(p.Leu85Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,611,492 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. L85L) has been classified as Likely benign.
Frequency
Consequence
NM_031372.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HNRNPDL | NM_031372.4 | c.253C>T | p.Leu85Phe | missense_variant | 1/8 | ENST00000295470.10 | |
HNRNPDL | NM_001207000.1 | c.253C>T | p.Leu85Phe | missense_variant | 1/7 | ||
HNRNPDL | NR_003249.2 | n.788C>T | non_coding_transcript_exon_variant | 1/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HNRNPDL | ENST00000295470.10 | c.253C>T | p.Leu85Phe | missense_variant | 1/8 | 1 | NM_031372.4 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152048Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000417 AC: 10AN: 239762Hom.: 0 AF XY: 0.0000381 AC XY: 5AN XY: 131310
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1459444Hom.: 1 Cov.: 33 AF XY: 0.0000152 AC XY: 11AN XY: 725968
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152048Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74258
ClinVar
Submissions by phenotype
Autosomal dominant limb-girdle muscular dystrophy type 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 30, 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 missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 464385). This missense change has been observed in individual(s) with clinical features of limb-girdle muscular dystrophy (Invitae). This variant is present in population databases (rs760917145, gnomAD 0.01%), including at least one homozygous and/or hemizygous individual. This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 85 of the HNRNPDL protein (p.Leu85Phe). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at