21-46430241-G-C

Variant names:

• chr21-46430241-G-C
• rs1023160
• NM_006031.6:c.7913+9G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006031.6(PCNT):​c.7913+9G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0908 in 1,608,684 control chromosomes in the GnomAD database, including 12,242 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (4500 hom., cov: 33)
  • Exomes 𝑓: 0.082 (7742 hom.)
• Consequence: PCNT NM_006031.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.337

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]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 21-46430241-G-C is Benign according to our data. Variant chr21-46430241-G-C is described in ClinVar as [Benign]. Clinvar id is 138608.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46430241-G-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCNT	NM_006031.6	c.7913+9G>C		intron_variant	Intron 36 of 46	ENST00000359568.10	NP_006022.3
PCNT	NM_001315529.2	c.7559+9G>C		intron_variant	Intron 36 of 46		NP_001302458.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCNT	ENST00000359568.10	c.7913+9G>C		intron_variant	Intron 36 of 46	1	NM_006031.6	ENSP00000352572.5

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27095 AN: 152058 Hom.: 4494 Cov.: 33

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0942

Gnomad ASJ AF: 0.0865

Gnomad EAS AF: 0.00559

Gnomad SAS AF: 0.0902

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0762

Gnomad OTH AF: 0.164

GnomAD2 exomes AF: 0.0958 AC: 23762 AN: 247964 AF XY: 0.0904

Gnomad AFR exome AF: 0.450

Gnomad AMR exome AF: 0.0548

Gnomad ASJ exome AF: 0.0865

Gnomad EAS exome AF: 0.00311

Gnomad FIN exome AF: 0.109

Gnomad NFE exome AF: 0.0747

Gnomad OTH exome AF: 0.0827

GnomAD4 exome AF: 0.0816 AC: 118900 AN: 1456508 Hom.: 7742 Cov.: 30 AF XY: 0.0807 AC XY: 58502 AN XY: 724686

African (AFR) AF: 0.462 AC: 15391 AN: 33312

American (AMR) AF: 0.0593 AC: 2642 AN: 44582

Ashkenazi Jewish (ASJ) AF: 0.0849 AC: 2215 AN: 26096

East Asian (EAS) AF: 0.00169 AC: 67 AN: 39672

South Asian (SAS) AF: 0.0841 AC: 7235 AN: 86060

European-Finnish (FIN) AF: 0.103 AC: 5465 AN: 52850

Middle Eastern (MID) AF: 0.0738 AC: 366 AN: 4958

European-Non Finnish (NFE) AF: 0.0719 AC: 79668 AN: 1108800

Other (OTH) AF: 0.0972 AC: 5851 AN: 60178

GnomAD4 genome AF: 0.178 AC: 27135 AN: 152176 Hom.: 4500 Cov.: 33 AF XY: 0.175 AC XY: 13005 AN XY: 74396

African (AFR) AF: 0.439 AC: 18217 AN: 41464

American (AMR) AF: 0.0940 AC: 1438 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0865 AC: 300 AN: 3470

East Asian (EAS) AF: 0.00560 AC: 29 AN: 5180

South Asian (SAS) AF: 0.0900 AC: 434 AN: 4820

European-Finnish (FIN) AF: 0.107 AC: 1134 AN: 10620

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0761 AC: 5177 AN: 68002

Other (OTH) AF: 0.167 AC: 353 AN: 2112

Alfa AF: 0.0745 Hom.: 232

Bravo AF: 0.189

Asia WGS AF: 0.104 AC: 362 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 26, 2014

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Microcephalic osteodysplastic primordial dwarfism type II Benign:1

Jan 13, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.35
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

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

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Other links and lift over

dbSNP: rs1023160; hg19: chr21-47850155; COSMIC: COSV64029129; COSMIC: COSV64029129;