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GeneBe

21-45941676-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001384156.1(PCBP3):c.1086G>A(p.Thr362=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.003 in 1,606,558 control chromosomes in the GnomAD database, including 122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 73 hom., cov: 33)
Exomes 𝑓: 0.0016 ( 49 hom. )

Consequence

PCBP3
NM_001384156.1 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.740
Variant links:
Genes affected
PCBP3 (HGNC:8651): (poly(rC) binding protein 3) This gene encodes a member of the KH-domain protein subfamily. Proteins of this subfamily, also referred to as alpha-CPs, bind to RNA with a specificity for C-rich pyrimidine regions. Alpha-CPs play important roles in post-transcriptional activities and have different cellular distributions. The protein encoded by this gene lacks the nuclear localization signals found in other subfamily members. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jan 2017]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.22).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 21-45941676-G-A is Benign according to our data. Variant chr21-45941676-G-A is described in ClinVar as [Benign]. Clinvar id is 781522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.74 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0538 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PCBP3NM_001384156.1 linkuse as main transcriptc.1086G>A p.Thr362= synonymous_variant 18/18 ENST00000681687.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PCBP3ENST00000681687.1 linkuse as main transcriptc.1086G>A p.Thr362= synonymous_variant 18/18 NM_001384156.1 P4P57721-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0161
AC:
2443
AN:
152052
Hom.:
72
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0558
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00661
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000162
Gnomad OTH
AF:
0.0110
GnomAD3 exomes
AF:
0.00417
AC:
1008
AN:
241590
Hom.:
21
AF XY:
0.00300
AC XY:
394
AN XY:
131286
show subpopulations
Gnomad AFR exome
AF:
0.0552
Gnomad AMR exome
AF:
0.00413
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000686
Gnomad FIN exome
AF:
0.0000931
Gnomad NFE exome
AF:
0.000181
Gnomad OTH exome
AF:
0.00156
GnomAD4 exome
AF:
0.00163
AC:
2375
AN:
1454388
Hom.:
49
Cov.:
30
AF XY:
0.00140
AC XY:
1016
AN XY:
723370
show subpopulations
Gnomad4 AFR exome
AF:
0.0538
Gnomad4 AMR exome
AF:
0.00452
Gnomad4 ASJ exome
AF:
0.0000385
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000106
Gnomad4 FIN exome
AF:
0.0000375
Gnomad4 NFE exome
AF:
0.000124
Gnomad4 OTH exome
AF:
0.00379
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0161
AC:
2446
AN:
152170
Hom.:
73
Cov.:
33
AF XY:
0.0157
AC XY:
1165
AN XY:
74382
show subpopulations
Gnomad4 AFR
AF:
0.0557
Gnomad4 AMR
AF:
0.00660
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.0109
Alfa
AF:
0.00124
Hom.:
0
Bravo
AF:
0.0184
Asia WGS
AF:
0.00289
AC:
10
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

PCBP3-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesNov 25, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJun 21, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.22
Cadd
Benign
6.5
Dann
Benign
0.71

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs61736689; hg19: chr21-47361590; COSMIC: COSV68408285; COSMIC: COSV68408285; API