chr4-82429443-G-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_031372.4(HNRNPDL):​c.248C>A​(p.Pro83Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000932 in 1,609,924 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 0.000040 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

HNRNPDL
NM_031372.4 missense

Scores

3
3
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.94
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 Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.38098165).
BS2
High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HNRNPDLNM_031372.4 linkuse as main transcriptc.248C>A p.Pro83Gln missense_variant 1/8 ENST00000295470.10 NP_112740.1
HNRNPDLNM_001207000.1 linkuse as main transcriptc.248C>A p.Pro83Gln missense_variant 1/7 NP_001193929.1
HNRNPDLNR_003249.2 linkuse as main transcriptn.783C>A 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.248C>A p.Pro83Gln missense_variant 1/81 NM_031372.4 ENSP00000295470 P4O14979-1

Frequencies

GnomAD3 genomes
AF:
0.0000396
AC:
6
AN:
151694
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000968
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000295
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000126
AC:
3
AN:
237318
Hom.:
0
AF XY:
0.00000768
AC XY:
1
AN XY:
130142
show subpopulations
Gnomad AFR exome
AF:
0.0000695
Gnomad AMR exome
AF:
0.00
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:
0.0000192
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000617
AC:
9
AN:
1458230
Hom.:
0
Cov.:
33
AF XY:
0.00000689
AC XY:
5
AN XY:
725278
show subpopulations
Gnomad4 AFR exome
AF:
0.0000900
Gnomad4 AMR exome
AF:
0.00
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:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000396
AC:
6
AN:
151694
Hom.:
0
Cov.:
32
AF XY:
0.0000270
AC XY:
2
AN XY:
74076
show subpopulations
Gnomad4 AFR
AF:
0.0000968
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000295
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227
ExAC
AF:
0.00000830
AC:
1

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 testingRevvity Omics, RevvityJan 31, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.29
CADD
Pathogenic
29
DANN
Uncertain
0.98
DEOGEN2
Benign
0.040
T;T;T
Eigen
Benign
-0.27
Eigen_PC
Benign
-0.18
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Benign
0.76
.;T;T
M_CAP
Pathogenic
0.90
D
MetaRNN
Benign
0.38
T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.0
N;N;.
MutationTaster
Benign
0.90
N;N
PrimateAI
Pathogenic
0.92
D
PROVEAN
Benign
-0.63
N;.;.
REVEL
Benign
0.12
Sift
Pathogenic
0.0
D;.;.
Sift4G
Uncertain
0.0030
D;D;D
Polyphen
0.86
P;P;.
Vest4
0.51
MutPred
0.26
Gain of helix (P = 0.0022);Gain of helix (P = 0.0022);Gain of helix (P = 0.0022);
MVP
0.66
MPC
1.3
ClinPred
0.41
T
GERP RS
2.5
Varity_R
0.25
gMVP
0.23

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs201774571; hg19: chr4-83350596; API