rs1362920184

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031372.4(HNRNPDL):c.35C>T(p.Pro12Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000165 in 1,214,454 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 (★). Synonymous variant affecting the same amino acid position (i.e. P12P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

HNRNPDL
NM_031372.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.06

Publications

0 publications found

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]

HNRNPDL Gene-Disease associations (from GenCC):

autosomal dominant limb-girdle muscular dystrophy type 1G
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
muscular dystrophy, limb-girdle, autosomal dominant
Inheritance: AD Classification: MODERATE Submitted by: ClinGen

HNRNPDL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23809832).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNRNPDL	NM_031372.4 link	c.35C>T	p.Pro12Leu	missense_variant	Exon 1 of 8	ENST00000295470.10	NP_112740.1	O14979-1A0A024RDB5
HNRNPDL	NM_001207000.1 link	c.35C>T	p.Pro12Leu	missense_variant	Exon 1 of 7		NP_001193929.1	O14979A0A087WUK2
HNRNPDL	NR_003249.2 link	n.570C>T		non_coding_transcript_exon_variant	Exon 1 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNRNPDL	ENST00000295470.10 link	c.35C>T	p.Pro12Leu	missense_variant	Exon 1 of 8	1	NM_031372.4	ENSP00000295470.5		O14979-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000165

AC:

AN:

1214454

Hom.:

Cov.:

AF XY:

0.00000170

AC XY:

AN XY:

586524

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

23614

American (AMR)

AF:

0.00

AC:

AN:

9978

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16438

East Asian (EAS)

AF:

0.00

AC:

AN:

27972

South Asian (SAS)

AF:

0.00

AC:

AN:

50948

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39208

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3706

European-Non Finnish (NFE)

AF:

0.00000201

AC:

AN:

992938

Other (OTH)

AF:

0.00

AC:

AN:

49652

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000081), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.300

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

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

Aug 16, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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: 533021). This variant has not been reported in the literature in individuals affected with HNRNPDL-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 12 of the HNRNPDL protein (p.Pro12Leu). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Uncertain

0.018

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

T;T;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.15

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.84

.;T;T

M_CAP

Pathogenic

0.77

MetaRNN

Benign

0.24

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

N;N;.

PhyloP100

3.1

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.15

N;.;.

REVEL

Benign

0.20

Sift

Pathogenic

0.0

D;.;.

Polyphen

0.61

P;P;.

Vest4

0.39

MutPred

0.12

Loss of glycosylation at P16 (P = 0.0242);Loss of glycosylation at P16 (P = 0.0242);Loss of glycosylation at P16 (P = 0.0242);

MVP

0.72

MPC

1.2

ClinPred

0.66

GERP RS

2.5

PromoterAI

-0.35

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.21

gMVP

0.21

Mutation Taster

=84/16

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over