Variant 19-41264553-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_007040.6(HNRNPUL1):c.50G>C(p.Arg17Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000329 in 1,519,000 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 (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

HNRNPUL1
NM_007040.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.83

Variant links:

Genes affected

HNRNPUL1 (HGNC:17011): (heterogeneous nuclear ribonucleoprotein U like 1) This gene encodes a nuclear RNA-binding protein of the heterogeneous nuclear ribonucleoprotein (hnRNP) family. This protein binds specifically to adenovirus early-1B-55kDa oncoprotein. It may play an important role in nucleocytoplasmic RNA transport, and its function is modulated by early-1B-55kDa in adenovirus-infected cells. [provided by RefSeq, Mar 2016]

HNRNPUL1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36198878).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HNRNPUL1	NM_007040.6 link	c.50G>C	p.Arg17Pro	missense_variant	1/15	ENST00000392006.8	NP_008971.2	Q9BUJ2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNRNPUL1	ENST00000392006.8 link	c.50G>C	p.Arg17Pro	missense_variant	1/15	1	NM_007040.6	ENSP00000375863.2		Q9BUJ2-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000293

AC:

AN:

1366764

Hom.:

Cov.:

AF XY:

0.00000149

AC XY:

AN XY:

673388

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000374

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 24, 2024

The c.50G>C (p.R17P) alteration is located in exon 1 (coding exon 1) of the HNRNPUL1 gene. This alteration results from a G to C substitution at nucleotide position 50, causing the arginine (R) at amino acid position 17 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

Pathogenic

0.99

BayesDel_addAF

Uncertain

0.040

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

T;.;T;.;T

Eigen

Benign

0.19

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.74

LIST_S2

Pathogenic

0.98

D;D;.;D;D

M_CAP

Pathogenic

0.48

MetaRNN

Benign

0.36

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;M;.;M;.

PrimateAI

Pathogenic

0.94

PROVEAN

Uncertain

-2.6

D;N;.;.;.

REVEL

Benign

0.19

Sift

Uncertain

0.0040

D;D;.;.;.

Sift4G

Uncertain

0.010

D;D;D;D;D

Polyphen

0.77

P;P;.;P;.

Vest4

0.47

MutPred

0.54

Loss of MoRF binding (P = 7e-04);Loss of MoRF binding (P = 7e-04);Loss of MoRF binding (P = 7e-04);Loss of MoRF binding (P = 7e-04);Loss of MoRF binding (P = 7e-04);

MVP

0.48

MPC

1.0

ClinPred

0.97

GERP RS

2.4

Varity_R

0.67

gMVP

0.79

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over