Variant 1-23310548-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The ENST00000302271.11(HNRNPR):c.1808C>T(p.Pro603Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

HNRNPR
ENST00000302271.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.94

Variant links:

Genes affected

HNRNPR (HGNC:5047): (heterogeneous nuclear ribonucleoprotein R) This gene encodes an RNA-binding protein that is a member of the spliceosome C complex, which functions in pre-mRNA processing and transport. The encoded protein also promotes transcription at the c-fos gene. Alternative splicing results in multiple transcript variants. There are pseudogenes for this gene on chromosomes 4, 11, and 10. [provided by RefSeq, Jul 2014]

HNRNPR links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), HNRNPR. . Gene score misZ 3.5388 (greater than the threshold 3.09). Trascript score misZ 4.0437 (greater than threshold 3.09). GenCC has associacion of gene with intellectual disability, autosomal dominant 40, syndromic intellectual disability, neurodevelopmental disorder with dysmorphic facies and skeletal and brain abnormalities.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HNRNPR	NM_005826.5 linkuse as main transcript	c.1808C>T	p.Pro603Leu	missense_variant	11/11	ENST00000302271.11	NP_005817.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNRNPR	ENST00000302271.11 linkuse as main transcript	c.1808C>T	p.Pro603Leu	missense_variant	11/11	1	NM_005826.5	ENSP00000304405	P3	O43390-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727238

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:

0.0000187

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

HNRNPR-related disorder

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 19, 2022

The HNRNPR c.1817C>T variant is predicted to result in the amino acid substitution p.Pro606Leu. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Uncertain

0.078

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.59

.;.;D;D;T;.

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Uncertain

0.97

M_CAP

Benign

0.074

MetaRNN

Uncertain

0.46

T;T;T;T;T;T

MetaSVM

Benign

-0.69

MutationAssessor

Uncertain

2.7

.;.;M;M;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Pathogenic

0.85

PROVEAN

Pathogenic

-4.5

.;D;D;D;.;D

REVEL

Uncertain

0.35

Sift

Uncertain

0.0010

.;D;D;D;.;D

Sift4G

Uncertain

0.0020

D;D;D;D;D;D

Polyphen

1.0

.;D;D;D;D;.

Vest4

0.63

MutPred

0.32

.;.;Gain of stability (P = 0.0053);Gain of stability (P = 0.0053);.;.;

MVP

0.67

MPC

0.61

ClinPred

1.0

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.46

gMVP

0.81

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