chr1-23961617-G-A
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_017761.4(PNRC2):c.160G>A(p.Ala54Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000112 in 1,613,938 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00012 ( 2 hom. )
Consequence
PNRC2
NM_017761.4 missense
NM_017761.4 missense
Scores
2
12
Clinical Significance
Conservation
PhyloP100: 6.80
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.086693615).
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PNRC2 | NM_017761.4 | c.160G>A | p.Ala54Thr | missense_variant | 3/3 | ENST00000334351.8 | |
PNRC2 | XM_017001691.1 | c.160G>A | p.Ala54Thr | missense_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PNRC2 | ENST00000334351.8 | c.160G>A | p.Ala54Thr | missense_variant | 3/3 | 1 | NM_017761.4 | P1 | |
PNRC2 | ENST00000374468.1 | c.160G>A | p.Ala54Thr | missense_variant | 3/3 | 2 | P1 | ||
PNRC2 | ENST00000647887.1 | c.160G>A | p.Ala54Thr | missense_variant | 4/4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152184Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000246 AC: 10AN: 40642Hom.: 1 AF XY: 0.000293 AC XY: 6AN XY: 20502
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GnomAD4 exome AF: 0.000117 AC: 171AN: 1461636Hom.: 2 Cov.: 33 AF XY: 0.000176 AC XY: 128AN XY: 727120
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GnomAD4 genome AF: 0.0000657 AC: 10AN: 152302Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74490
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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 | Jul 09, 2021 | The c.160G>A (p.A54T) alteration is located in exon 3 (coding exon 1) of the PNRC2 gene. This alteration results from a G to A substitution at nucleotide position 160, causing the alanine (A) at amino acid position 54 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;N
MutationTaster
Benign
D;D
PrimateAI
Benign
T
Polyphen
B;B;B
Vest4
0.17, 0.18
MutPred
Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);
MVP
0.34
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at