dbSNP rs189841383: HNRNPDL:p.Pro19Pro (chr4-82429634-G-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_031372.4(HNRNPDL):c.57C>T(p.Pro19Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000164 in 1,221,110 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 (★). Synonymous variant affecting the same amino acid position (i.e. P19P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

HNRNPDL
NM_031372.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.90

Publications

1 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: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 4-82429634-G-A is Benign according to our data. Variant chr4-82429634-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 464390.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.9 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
HNRNPDL	NM_031372.4 link	c.57C>T	p.Pro19Pro	synonymous_variant	Exon 1 of 8	ENST00000295470.10	NP_112740.1
HNRNPDL	NM_001207000.1 link	c.57C>T	p.Pro19Pro	synonymous_variant	Exon 1 of 7		NP_001193929.1
HNRNPDL	NR_003249.2 link	n.592C>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.57C>T	p.Pro19Pro	synonymous_variant	Exon 1 of 8	1	NM_031372.4	ENSP00000295470.5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000164

AC:

AN:

1221110

Hom.:

Cov.:

AF XY:

0.00000169

AC XY:

AN XY:

590892

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23616

American (AMR)

AF:

0.00

AC:

AN:

10036

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16560

East Asian (EAS)

AF:

0.0000357

AC:

AN:

28046

South Asian (SAS)

AF:

0.00

AC:

AN:

52210

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40018

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3656

European-Non Finnish (NFE)

AF:

0.00000100

AC:

AN:

997110

Other (OTH)

AF:

0.00

AC:

AN:

49858

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Autosomal dominant limb-girdle muscular dystrophy type 1G

Benign:1

May 31, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.96

PhyloP100

2.9

PromoterAI

0.034

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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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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