rs61735805

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_006031.6(PCNT):​c.3339T>C​(p.Ser1113Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.042 in 1,614,146 control chromosomes in the GnomAD database, including 1,665 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 100 hom., cov: 33)
Exomes 𝑓: 0.043 ( 1565 hom. )

Consequence

PCNT
NM_006031.6 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.537
Variant links:
Genes affected
PCNT (HGNC:16068): (pericentrin) The protein encoded by this gene binds to calmodulin and is expressed in the centrosome. It is an integral component of the pericentriolar material (PCM). The protein contains a series of coiled-coil domains and a highly conserved PCM targeting motif called the PACT domain near its C-terminus. The protein interacts with the microtubule nucleation component gamma-tubulin and is likely important to normal functioning of the centrosomes, cytoskeleton, and cell-cycle progression. Mutations in this gene cause Seckel syndrome-4 and microcephalic osteodysplastic primordial dwarfism type II. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
Variant 21-46385858-T-C is Benign according to our data. Variant chr21-46385858-T-C is described in ClinVar as [Benign]. Clinvar id is 159585.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46385858-T-C is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-0.537 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0306 (4659/152312) while in subpopulation NFE AF= 0.0486 (3305/68022). AF 95% confidence interval is 0.0472. There are 100 homozygotes in gnomad4. There are 2189 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 100 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PCNTNM_006031.6 linkc.3339T>C p.Ser1113Ser synonymous_variant Exon 17 of 47 ENST00000359568.10 NP_006022.3 O95613-1
PCNTNM_001315529.2 linkc.2985T>C p.Ser995Ser synonymous_variant Exon 17 of 47 NP_001302458.1 O95613-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PCNTENST00000359568.10 linkc.3339T>C p.Ser1113Ser synonymous_variant Exon 17 of 47 1 NM_006031.6 ENSP00000352572.5 O95613-1

Frequencies

GnomAD3 genomes
AF:
0.0306
AC:
4660
AN:
152194
Hom.:
99
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00770
Gnomad AMI
AF:
0.0406
Gnomad AMR
AF:
0.0191
Gnomad ASJ
AF:
0.0458
Gnomad EAS
AF:
0.000961
Gnomad SAS
AF:
0.0251
Gnomad FIN
AF:
0.0333
Gnomad MID
AF:
0.0475
Gnomad NFE
AF:
0.0486
Gnomad OTH
AF:
0.0258
GnomAD3 exomes
AF:
0.0355
AC:
8923
AN:
251494
Hom.:
208
AF XY:
0.0368
AC XY:
4996
AN XY:
135920
show subpopulations
Gnomad AFR exome
AF:
0.00757
Gnomad AMR exome
AF:
0.0198
Gnomad ASJ exome
AF:
0.0467
Gnomad EAS exome
AF:
0.00125
Gnomad SAS exome
AF:
0.0320
Gnomad FIN exome
AF:
0.0388
Gnomad NFE exome
AF:
0.0492
Gnomad OTH exome
AF:
0.0337
GnomAD4 exome
AF:
0.0432
AC:
63162
AN:
1461834
Hom.:
1565
Cov.:
32
AF XY:
0.0433
AC XY:
31484
AN XY:
727220
show subpopulations
Gnomad4 AFR exome
AF:
0.00621
Gnomad4 AMR exome
AF:
0.0205
Gnomad4 ASJ exome
AF:
0.0443
Gnomad4 EAS exome
AF:
0.000781
Gnomad4 SAS exome
AF:
0.0342
Gnomad4 FIN exome
AF:
0.0401
Gnomad4 NFE exome
AF:
0.0478
Gnomad4 OTH exome
AF:
0.0399
GnomAD4 genome
AF:
0.0306
AC:
4659
AN:
152312
Hom.:
100
Cov.:
33
AF XY:
0.0294
AC XY:
2189
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.00767
Gnomad4 AMR
AF:
0.0190
Gnomad4 ASJ
AF:
0.0458
Gnomad4 EAS
AF:
0.000963
Gnomad4 SAS
AF:
0.0253
Gnomad4 FIN
AF:
0.0333
Gnomad4 NFE
AF:
0.0486
Gnomad4 OTH
AF:
0.0255
Alfa
AF:
0.0441
Hom.:
83
Bravo
AF:
0.0282
Asia WGS
AF:
0.0130
AC:
44
AN:
3478
EpiCase
AF:
0.0467
EpiControl
AF:
0.0424

ClinVar

Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Feb 02, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Mar 03, 2015
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Microcephalic osteodysplastic primordial dwarfism type II Benign:3
Jan 12, 2018
Illumina Laboratory Services, Illumina
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jun 28, 2017
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

not specified Benign:1
Feb 08, 2013
Genetic Services Laboratory, University of Chicago
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
0.67
DANN
Benign
0.40

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: rs61735805; hg19: chr21-47805773; API