chr4-82429581-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_031372.4(HNRNPDL):c.110A>C(p.Gln37Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,383,816 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00062 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 1 hom. )

Consequence

HNRNPDL
NM_031372.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: 0.966

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 -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14141434).

BP6

Variant 4-82429581-T-G is Benign according to our data. Variant chr4-82429581-T-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 464378.

BS2

High AC in GnomAd4 at 93 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNRNPDL	NM_031372.4 link	c.110A>C	p.Gln37Pro	missense_variant	Exon 1 of 8	ENST00000295470.10	NP_112740.1	O14979-1A0A024RDB5
HNRNPDL	NM_001207000.1 link	c.110A>C	p.Gln37Pro	missense_variant	Exon 1 of 7		NP_001193929.1	O14979A0A087WUK2
HNRNPDL	NR_003249.2 link	n.645A>C		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.110A>C	p.Gln37Pro	missense_variant	Exon 1 of 8	1	NM_031372.4	ENSP00000295470.5		O14979-1

Frequencies

GnomAD3 genomes

AF:

0.000617

AC:

AN:

150670

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000343

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.000290

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00109

Gnomad OTH

AF:

0.000484

GnomAD2 exomes

AF:

0.000306

AC:

AN:

16354

AF XY:

0.000480

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:

0.000770

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00108

AC:

1336

AN:

1233046

Hom.:

Cov.:

AF XY:

0.00104

AC XY:

625

AN XY:

598706

show subpopulations

African (AFR)

AF:

0.000257

AC:

AN:

23382

American (AMR)

AF:

0.000280

AC:

AN:

10732

Ashkenazi Jewish (ASJ)

AF:

0.000178

AC:

AN:

16864

East Asian (EAS)

AF:

0.00

AC:

AN:

28358

South Asian (SAS)

AF:

0.000147

AC:

AN:

54568

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39306

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3570

European-Non Finnish (NFE)

AF:

0.00127

AC:

1278

AN:

1005890

Other (OTH)

AF:

0.000754

AC:

AN:

50376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.423

Heterozygous variant carriers

157

235

314

392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

174

232

290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000617

AC:

AN:

150770

Hom.:

Cov.:

AF XY:

0.000421

AC XY:

AN XY:

73648

show subpopulations

African (AFR)

AF:

0.000342

AC:

AN:

40878

American (AMR)

AF:

0.000197

AC:

AN:

15232

Ashkenazi Jewish (ASJ)

AF:

0.000290

AC:

AN:

3454

East Asian (EAS)

AF:

0.00

AC:

AN:

4972

South Asian (SAS)

AF:

0.00

AC:

AN:

4796

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10534

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.00109

AC:

AN:

67624

Other (OTH)

AF:

0.000478

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000857

Hom.:

ExAC

AF:

0.0000502

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Autosomal dominant limb-girdle muscular dystrophy type 1G

Uncertain:1Benign:1

Jan 13, 2022

Revvity Omics, Revvity

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 15, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Uncertain:1

Jul 19, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.110A>C (p.Q37P) alteration is located in exon 1 (coding exon 1) of the HNRNPDL gene. This alteration results from a A to C substitution at nucleotide position 110, causing the glutamine (Q) at amino acid position 37 to be replaced by a proline (P). 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

0.060

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.018

T;T;T

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.39

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.74

.;T;T

M_CAP

Pathogenic

0.75

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N;.

PhyloP100

0.97

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.060

N;.;.

REVEL

Benign

0.19

Sift

Pathogenic

0.0

D;.;.

Polyphen

0.0040

B;B;.

Vest4

0.39

MVP

0.70

MPC

0.93

ClinPred

0.36

GERP RS

1.7

PromoterAI

0.020

Neutral

(source)

Varity_R

0.34

gMVP

0.21

Mutation Taster

=94/6

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

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over