1-23961597-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017761.4(PNRC2):ā€‹c.140A>Gā€‹(p.His47Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000589 in 1,613,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00060 ( 0 hom., cov: 33)
Exomes š‘“: 0.00059 ( 0 hom. )

Consequence

PNRC2
NM_017761.4 missense

Scores

2
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.53
Variant links:
Genes affected
PNRC2 (HGNC:23158): (proline rich nuclear receptor coactivator 2) Involved in nuclear-transcribed mRNA catabolic process, nonsense-mediated decay. Located in Golgi apparatus; P-body; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.037103146).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PNRC2NM_017761.4 linkuse as main transcriptc.140A>G p.His47Arg missense_variant 3/3 ENST00000334351.8
PNRC2XM_017001691.1 linkuse as main transcriptc.140A>G p.His47Arg missense_variant 3/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PNRC2ENST00000334351.8 linkuse as main transcriptc.140A>G p.His47Arg missense_variant 3/31 NM_017761.4 P1Q9NPJ4-1
PNRC2ENST00000374468.1 linkuse as main transcriptc.140A>G p.His47Arg missense_variant 3/32 P1Q9NPJ4-1
PNRC2ENST00000647887.1 linkuse as main transcriptc.140A>G p.His47Arg missense_variant 4/4 P1Q9NPJ4-1

Frequencies

GnomAD3 genomes
AF:
0.000604
AC:
92
AN:
152216
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00209
Gnomad ASJ
AF:
0.00231
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000188
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000647
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000329
AC:
13
AN:
39496
Hom.:
0
AF XY:
0.000301
AC XY:
6
AN XY:
19922
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000984
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:
0.000417
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000587
AC:
858
AN:
1461594
Hom.:
0
Cov.:
33
AF XY:
0.000582
AC XY:
423
AN XY:
727108
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000939
Gnomad4 ASJ exome
AF:
0.00142
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.000318
Gnomad4 NFE exome
AF:
0.000646
Gnomad4 OTH exome
AF:
0.000530
GnomAD4 genome
AF:
0.000604
AC:
92
AN:
152216
Hom.:
0
Cov.:
33
AF XY:
0.000565
AC XY:
42
AN XY:
74380
show subpopulations
Gnomad4 AFR
AF:
0.000121
Gnomad4 AMR
AF:
0.00209
Gnomad4 ASJ
AF:
0.00231
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.000647
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000356
Hom.:
0
Bravo
AF:
0.000491
ExAC
AF:
0.0000766
AC:
1

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 submitterclinical testingAmbry GeneticsApr 27, 2022The c.140A>G (p.H47R) alteration is located in exon 3 (coding exon 1) of the PNRC2 gene. This alteration results from a A to G substitution at nucleotide position 140, causing the histidine (H) at amino acid position 47 to be replaced by an arginine (R). 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
Benign
0.071
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
21
DANN
Benign
0.94
DEOGEN2
Benign
0.13
T;T;T
Eigen
Benign
-0.25
Eigen_PC
Benign
-0.11
FATHMM_MKL
Uncertain
0.81
D
M_CAP
Benign
0.0035
T
MetaRNN
Benign
0.037
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.0
L;L;L
MutationTaster
Benign
0.52
N;N
PrimateAI
Uncertain
0.67
T
Polyphen
0.0
B;B;B
Vest4
0.13, 0.17
MutPred
0.21
Gain of methylation at H47 (P = 0.0248);Gain of methylation at H47 (P = 0.0248);Gain of methylation at H47 (P = 0.0248);
MVP
0.38
ClinPred
0.069
T
GERP RS
3.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.15
gMVP
0.33

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: rs779697948; hg19: chr1-24288087; API