rs771120108

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_031372.4(HNRNPDL):c.114A>G(p.Leu38Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000171 in 1,389,594 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

HNRNPDL
NM_031372.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.101

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: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 4-82429577-T-C is Benign according to our data. Variant chr4-82429577-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 464380.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.101 with no splicing effect.

BS2

High AC in GnomAd4 at 24 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNRNPDL	NM_031372.4 link	c.114A>G	p.Leu38Leu	synonymous_variant	Exon 1 of 8	ENST00000295470.10	NP_112740.1	O14979-1A0A024RDB5
HNRNPDL	NM_001207000.1 link	c.114A>G	p.Leu38Leu	synonymous_variant	Exon 1 of 7		NP_001193929.1	O14979A0A087WUK2
HNRNPDL	NR_003249.2 link	n.649A>G		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.114A>G	p.Leu38Leu	synonymous_variant	Exon 1 of 8	1	NM_031372.4	ENSP00000295470.5		O14979-1

Frequencies

GnomAD3 genomes

AF:

0.000159

AC:

AN:

151356

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000728

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000947

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000266

Gnomad OTH

AF:

0.000481

GnomAD2 exomes

AF:

0.0000512

AC:

AN:

19536

AF XY:

0.0000998

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000129

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000172

AC:

213

AN:

1238238

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

601588

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23750

American (AMR)

AF:

0.00

AC:

AN:

11010

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16976

East Asian (EAS)

AF:

0.00

AC:

AN:

28470

South Asian (SAS)

AF:

0.00

AC:

AN:

55416

European-Finnish (FIN)

AF:

0.0000249

AC:

AN:

40164

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3644

European-Non Finnish (NFE)

AF:

0.000204

AC:

206

AN:

1008254

Other (OTH)

AF:

0.000119

AC:

AN:

50554

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000159

AC:

AN:

151356

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

AN XY:

73904

show subpopulations

African (AFR)

AF:

0.0000728

AC:

AN:

41226

American (AMR)

AF:

0.0000656

AC:

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5030

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.0000947

AC:

AN:

10562

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.000266

AC:

AN:

67716

Other (OTH)

AF:

0.000481

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000270

Hom.:

Bravo

AF:

0.0000680

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

HNRNPDL-related disorder

Benign:1

Dec 07, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Autosomal dominant limb-girdle muscular dystrophy type 1G

Benign:1

Oct 08, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

HNRNPDL: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

9.2

(source)

DANN

Benign

0.58

PhyloP100

-0.10

PromoterAI

-0.032

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

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

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rs771120108

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over