Variant 19-41264601-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_007040.6(HNRNPUL1):c.98T>C(p.Leu33Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000634 in 1,578,024 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

HNRNPUL1
NM_007040.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.11

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HNRNPUL1	NM_007040.6 link	c.98T>C	p.Leu33Pro	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.98T>C	p.Leu33Pro	missense_variant	1/15	1	NM_007040.6	ENSP00000375863.2		Q9BUJ2-1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000103

AC:

AN:

193874

Hom.:

AF XY:

0.00000921

AC XY:

AN XY:

108572

show subpopulations

Gnomad AFR exome

AF:

0.000207

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000281

AC:

AN:

1425812

Hom.:

Cov.:

AF XY:

0.00000282

AC XY:

AN XY:

708120

show subpopulations

Gnomad4 AFR exome

AF:

0.000126

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.000145

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.0000172

AC:

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 04, 2023

The c.98T>C (p.L33P) alteration is located in exon 1 (coding exon 1) of the HNRNPUL1 gene. This alteration results from a T to C substitution at nucleotide position 98, causing the leucine (L) at amino acid position 33 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

1.0

BayesDel_addAF

Pathogenic

0.35

BayesDel_noAF

Pathogenic

0.26

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.43

T;.;D;.;D

Eigen

Pathogenic

0.87

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Uncertain

0.97

LIST_S2

Pathogenic

0.99

D;T;.;D;D

M_CAP

Pathogenic

0.98

MetaRNN

Uncertain

0.72

D;D;D;D;D

MetaSVM

Uncertain

0.26

MutationAssessor

Pathogenic

3.6

H;H;.;H;.

PrimateAI

Pathogenic

0.94

PROVEAN

Uncertain

-4.3

D;D;.;.;.

REVEL

Uncertain

0.54

Sift

Pathogenic

0.0

D;D;.;.;.

Sift4G

Pathogenic

0.0010

D;D;D;D;D

Polyphen

1.0

D;D;.;D;.

Vest4

0.85

MutPred

0.65

Loss of stability (P = 0.0386);Loss of stability (P = 0.0386);Loss of stability (P = 0.0386);Loss of stability (P = 0.0386);Loss of stability (P = 0.0386);

MVP

0.87

MPC

1.1

ClinPred

0.96

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.95

gMVP

0.89

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