chr12-54280818-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 5P and 1B. PM1PM2PP2BP4
The NM_031157.4(HNRNPA1):c.11C>T(p.Ser4Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,876 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 Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
HNRNPA1
NM_031157.4 missense
NM_031157.4 missense
Scores
2
9
6
Clinical Significance
Conservation
PhyloP100: 3.81
Genes affected
HNRNPA1 (HGNC:5031): (heterogeneous nuclear ribonucleoprotein A1) This gene encodes a member of a family of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs), which are RNA-binding proteins that associate with pre-mRNAs in the nucleus and influence pre-mRNA processing, as well as other aspects of mRNA metabolism and transport. The protein encoded by this gene is one of the most abundant core proteins of hnRNP complexes and plays a key role in the regulation of alternative splicing. Mutations in this gene have been observed in individuals with amyotrophic lateral sclerosis 20. Multiple alternatively spliced transcript variants have been found. There are numerous pseudogenes of this gene distributed throughout the genome. [provided by RefSeq, Feb 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM1
?
In a modified_residue Phosphoserine (size 0) in uniprot entity ROA1_HUMAN
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, HNRNPA1
BP4
?
Computational evidence support a benign effect (MetaRNN=0.39346075).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HNRNPA1 | NM_031157.4 | c.11C>T | p.Ser4Leu | missense_variant | 1/11 | ENST00000340913.11 | |
HNRNPA1 | NM_002136.4 | c.11C>T | p.Ser4Leu | missense_variant | 1/10 | ||
HNRNPA1 | NR_135167.2 | n.93C>T | non_coding_transcript_exon_variant | 1/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HNRNPA1 | ENST00000340913.11 | c.11C>T | p.Ser4Leu | missense_variant | 1/11 | 1 | NM_031157.4 | ||
ENST00000553061.1 | n.545+3643C>T | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000800 AC: 2AN: 249930Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135572
GnomAD3 exomes
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461876Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 727238
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
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Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | May 13, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.;M;.;.;M
MutationTaster
Benign
D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D;D;D;D;D
REVEL
Uncertain
Sift
Benign
T;D;T;T;T;T
Sift4G
Benign
T;D;T;T;T;T
Polyphen
P;.;P;.;P;B
Vest4
MutPred
Loss of phosphorylation at S4 (P = 0.0028);Loss of phosphorylation at S4 (P = 0.0028);Loss of phosphorylation at S4 (P = 0.0028);Loss of phosphorylation at S4 (P = 0.0028);Loss of phosphorylation at S4 (P = 0.0028);Loss of phosphorylation at S4 (P = 0.0028);
MVP
MPC
1.7
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at