Variant 1-23310587-T-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.1769A>T(p.Asn590Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

HNRNPR
ENST00000302271.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.20

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.1769A>T	p.Asn590Ile	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.1769A>T	p.Asn590Ile	missense_variant	11/11	1	NM_005826.5	ENSP00000304405	P3	O43390-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

See cases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

New York Genome Center

Jul 17, 2020

The c.1778A>T (p.Asn593Ile) variant in exon 11 of 11 of HNRNPR has not been reported in affected individuals in the available literature. This variant is absent in gnomAD suggesting it is not a common benign variant in the populations represented in this database. In silico predictors suggest this variant is Neutral (Provean; score: -1.80) and Damaging (SIFT; score: 0.012). p.Asn593Ile variant seen in this individual is localized in the C-terminal QN domain (glutamine/asparagine-rich domain) similar to the previously reported missense variant seen in an affected individual [PMID: 31079900]. Given the current evidences regarding its pathogenicity, the c.1778A>T (p.Asn593Ile) variant identified in the HNRNPR gene is a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

0.010

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Benign

0.91

DEOGEN2

Benign

0.26

.;.;T;T;T;.

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.95

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.42

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

.;.;M;M;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.8

.;N;N;N;.;N

REVEL

Benign

0.18

Sift

Uncertain

0.012

.;D;D;D;.;D

Sift4G

Benign

0.14

T;T;T;T;T;T

Polyphen

0.95, 0.92

.;P;P;P;P;.

Vest4

0.58

MutPred

0.19

.;.;Gain of MoRF binding (P = 0.0842);Gain of MoRF binding (P = 0.0842);.;.;

MVP

0.54

MPC

0.74

ClinPred

0.83

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.29

gMVP

0.64

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over