1-23310998-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_005826.5(HNRNPR):​c.1358G>C​(p.Gly453Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000211 in 1,614,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

HNRNPR
NM_005826.5 missense

Scores

1
1
16

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.79
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.17348987).
BP6
Variant 1-23310998-C-G is Benign according to our data. Variant chr1-23310998-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3284582.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAdExome4 at 31 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HNRNPRNM_005826.5 linkc.1358G>C p.Gly453Ala missense_variant Exon 11 of 11 ENST00000302271.11 NP_005817.1 O43390-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HNRNPRENST00000302271.11 linkc.1358G>C p.Gly453Ala missense_variant Exon 11 of 11 1 NM_005826.5 ENSP00000304405.6 O43390-1
HNRNPRENST00000374616.7 linkc.1367G>C p.Gly456Ala missense_variant Exon 11 of 11 1 ENSP00000363745.3 O43390-2
HNRNPRENST00000478691.5 linkc.1064G>C p.Gly355Ala missense_variant Exon 10 of 10 1 ENSP00000474437.1 O43390-4

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152206
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000478
AC:
12
AN:
250822
Hom.:
0
AF XY:
0.0000738
AC XY:
10
AN XY:
135566
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000884
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000212
AC:
31
AN:
1461872
Hom.:
0
Cov.:
33
AF XY:
0.0000261
AC XY:
19
AN XY:
727232
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:
0.0000927
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000198
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152206
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.0000906
AC:
11
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Benign:1
May 06, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.40
CADD
Uncertain
23
DANN
Benign
0.84
DEOGEN2
Benign
0.29
.;.;T;T;T;.
Eigen
Benign
-0.21
Eigen_PC
Benign
-0.011
FATHMM_MKL
Pathogenic
0.97
D
M_CAP
Benign
0.0068
T
MetaRNN
Benign
0.17
T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.91
.;.;L;L;.;.
PrimateAI
Uncertain
0.67
T
PROVEAN
Benign
-1.0
.;N;N;N;.;N
REVEL
Benign
0.094
Sift
Benign
0.70
.;T;T;T;.;T
Sift4G
Benign
0.17
T;T;T;T;T;T
Polyphen
0.014, 0.0080, 0.0010
.;B;B;B;B;.
Vest4
0.53
MVP
0.39
MPC
0.64
ClinPred
0.072
T
GERP RS
4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8
Varity_R
0.26
gMVP
0.73

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.

Other links and lift over

dbSNP: rs776523472; hg19: chr1-23637491; API