rs1289857424

Variant summary

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

The NM_031372.4(HNRNPDL):​c.107G>T​(p.Arg36Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000218 in 1,376,714 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

HNRNPDL
NM_031372.4 missense

Scores

3
1
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.46
Variant links:
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]

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=0.15985703).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HNRNPDLNM_031372.4 linkuse as main transcriptc.107G>T p.Arg36Leu missense_variant 1/8 ENST00000295470.10 NP_112740.1 O14979-1A0A024RDB5
HNRNPDLNM_001207000.1 linkuse as main transcriptc.107G>T p.Arg36Leu missense_variant 1/7 NP_001193929.1 O14979A0A087WUK2
HNRNPDLNR_003249.2 linkuse as main transcriptn.642G>T non_coding_transcript_exon_variant 1/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HNRNPDLENST00000295470.10 linkuse as main transcriptc.107G>T p.Arg36Leu missense_variant 1/81 NM_031372.4 ENSP00000295470.5 O14979-1

Frequencies

GnomAD3 genomes
AF:
0.00000663
AC:
1
AN:
150764
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000657
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000805
AC:
1
AN:
12424
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
6422
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00105
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:
0.00000163
AC:
2
AN:
1225950
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
594642
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000192
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000663
AC:
1
AN:
150764
Hom.:
0
Cov.:
32
AF XY:
0.0000136
AC XY:
1
AN XY:
73590
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000657
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151

ClinVar

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

Submissions by phenotype

Autosomal dominant limb-girdle muscular dystrophy type 1G Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 31, 2023This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 36 of the HNRNPDL protein (p.Arg36Leu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 464377). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Benign
-0.061
T
BayesDel_noAF
Benign
-0.33
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.022
T;T;T
Eigen
Benign
-0.53
Eigen_PC
Benign
-0.37
FATHMM_MKL
Benign
0.72
D
LIST_S2
Benign
0.82
.;T;T
M_CAP
Pathogenic
0.87
D
MetaRNN
Benign
0.16
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N;N;.
PrimateAI
Pathogenic
0.94
D
PROVEAN
Benign
-0.27
N;.;.
REVEL
Benign
0.080
Sift
Pathogenic
0.0
D;.;.
Polyphen
0.0
B;B;.
Vest4
0.45
MutPred
0.29
Loss of glycosylation at P32 (P = 0.0063);Loss of glycosylation at P32 (P = 0.0063);Loss of glycosylation at P32 (P = 0.0063);
MVP
0.53
MPC
0.89
ClinPred
0.27
T
GERP RS
3.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.8
Varity_R
0.38
gMVP
0.36

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: rs1289857424; hg19: chr4-83350737; API