chr5-137753411-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006805.4(HNRNPA0):​c.656G>A​(p.Ser219Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000286 in 1,397,316 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 (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

HNRNPA0
NM_006805.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.49
Variant links:
Genes affected
HNRNPA0 (HGNC:5030): (heterogeneous nuclear ribonucleoprotein A0) This gene belongs to the A/B 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 repeats of quasi-RRM domains that bind RNAs, followed by a glycine-rich C-terminus. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.23980328).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HNRNPA0NM_006805.4 linkc.656G>A p.Ser219Asn missense_variant Exon 1 of 1 ENST00000314940.7 NP_006796.1 Q13151

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HNRNPA0ENST00000314940.7 linkc.656G>A p.Ser219Asn missense_variant Exon 1 of 1 6 NM_006805.4 ENSP00000316042.4 Q13151

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000136
AC:
2
AN:
147506
Hom.:
0
AF XY:
0.0000251
AC XY:
2
AN XY:
79630
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000812
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000286
AC:
4
AN:
1397316
Hom.:
0
Cov.:
32
AF XY:
0.00000290
AC XY:
2
AN XY:
689572
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000839
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.27e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000756
ExAC
AF:
0.00000996
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 23, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.656G>A (p.S219N) alteration is located in exon 1 (coding exon 1) of the HNRNPA0 gene. This alteration results from a G to A substitution at nucleotide position 656, causing the serine (S) at amino acid position 219 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
19
DANN
Benign
0.97
DEOGEN2
Benign
0.12
T
Eigen
Benign
-0.46
Eigen_PC
Benign
-0.27
FATHMM_MKL
Benign
0.45
N
LIST_S2
Benign
0.33
T
M_CAP
Pathogenic
0.66
D
MetaRNN
Benign
0.24
T
MetaSVM
Benign
-0.48
T
MutationAssessor
Benign
0.90
L
PrimateAI
Pathogenic
0.83
D
PROVEAN
Benign
0.0
N
REVEL
Benign
0.18
Sift
Benign
0.17
T
Sift4G
Benign
0.34
T
Polyphen
0.0020
B
Vest4
0.33
MutPred
0.31
Loss of phosphorylation at S219 (P = 0.0119);
MVP
0.64
MPC
1.3
ClinPred
0.10
T
GERP RS
4.6
Varity_R
0.067
gMVP
0.80

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs754153801; hg19: chr5-137089100; API