NM_006031.6:c.7800G>A

Variant names:

• chr21-46430119-G-A
• rs61735820
• NM_006031.6:c.7800G>A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_006031.6(PCNT):​c.7800G>A​(p.Ala2600Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0205 in 1,614,180 control chromosomes in the GnomAD database, including 456 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (20 hom., cov: 33)
  • Exomes 𝑓: 0.021 (436 hom.)
• Consequence: PCNT NM_006031.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.272

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

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 21-46430119-G-A is Benign according to our data. Variant chr21-46430119-G-A is described in ClinVar as [Benign]. Clinvar id is 138606.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46430119-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.272 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0145 (2212/152344) while in subpopulation NFE AF= 0.0245 (1669/68020). AF 95% confidence interval is 0.0236. There are 20 homozygotes in gnomad4. There are 986 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCNT	NM_006031.6	c.7800G>A	p.Ala2600Ala	synonymous_variant	Exon 36 of 47	ENST00000359568.10	NP_006022.3
PCNT	NM_001315529.2	c.7446G>A	p.Ala2482Ala	synonymous_variant	Exon 36 of 47		NP_001302458.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCNT	ENST00000359568.10	c.7800G>A	p.Ala2600Ala	synonymous_variant	Exon 36 of 47	1	NM_006031.6	ENSP00000352572.5

Frequencies

GnomAD3 genomes AF: 0.0145 AC: 2211 AN: 152226 Hom.: 20 Cov.: 33

Gnomad AFR AF: 0.00473

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0125

Gnomad ASJ AF: 0.00691

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00289

Gnomad FIN AF: 0.00725

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0245

Gnomad OTH AF: 0.0186

GnomAD3 exomes AF: 0.0138 AC: 3479 AN: 251398 Hom.: 36 AF XY: 0.0141 AC XY: 1914 AN XY: 135906

Gnomad AFR exome AF: 0.00382

Gnomad AMR exome AF: 0.00787

Gnomad ASJ exome AF: 0.00526

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00369

Gnomad FIN exome AF: 0.00739

Gnomad NFE exome AF: 0.0239

Gnomad OTH exome AF: 0.0160

GnomAD4 exome AF: 0.0212 AC: 30931 AN: 1461836 Hom.: 436 Cov.: 32 AF XY: 0.0207 AC XY: 15048 AN XY: 727220

Gnomad4 AFR exome AF: 0.00275

Gnomad4 AMR exome AF: 0.00921

Gnomad4 ASJ exome AF: 0.00539

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00429

Gnomad4 FIN exome AF: 0.00792

Gnomad4 NFE exome AF: 0.0256

Gnomad4 OTH exome AF: 0.0168

GnomAD4 genome AF: 0.0145 AC: 2212 AN: 152344 Hom.: 20 Cov.: 33 AF XY: 0.0132 AC XY: 986 AN XY: 74484

Gnomad4 AFR AF: 0.00471

Gnomad4 AMR AF: 0.0125

Gnomad4 ASJ AF: 0.00691

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00310

Gnomad4 FIN AF: 0.00725

Gnomad4 NFE AF: 0.0245

Gnomad4 OTH AF: 0.0184

Alfa AF: 0.0188 Hom.: 20

Bravo AF: 0.0147

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.0218

EpiControl AF: 0.0231

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

May 23, 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. -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Jan 27, 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:2

Oct 19, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	3.9
DANN	Benign	0.59

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

Other links and lift over

dbSNP: rs61735820; hg19: chr21-47850033;