rs11701058

Variant names:

• chr21-46356467-T-C
• rs11701058
• NM_006031.6:c.1937-507T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006031.6(PCNT):​c.1937-507T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,138 control chromosomes in the GnomAD database, including 2,981 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (2981 hom., cov: 34)
• Consequence: PCNT NM_006031.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• Publications: 13 publications found

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]

PCNT Gene-Disease associations (from GenCC):

• microcephalic osteodysplastic primordial dwarfism type II

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, G2P, Orphanet
• Moyamoya disease

  Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006031.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCNT	NM_006031.6	MANE Select	c.1937-507T>C		intron	N/A	NP_006022.3
	PCNT	NM_001315529.2		c.1583-507T>C		intron	N/A	NP_001302458.1	O95613-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCNT	ENST00000359568.10	TSL:1 MANE Select	c.1937-507T>C		intron	N/A	ENSP00000352572.5	O95613-1
	PCNT	ENST00000480896.5	TSL:1	c.1583-507T>C		intron	N/A	ENSP00000511989.1	O95613-2
	PCNT	ENST00000695558.1		c.1937-507T>C		intron	N/A	ENSP00000512015.1	A0A8Q3SHZ3

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27641 AN: 152018 Hom.: 2980 Cov.: 34

Gnomad AFR AF: 0.0745

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.201

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.182 AC: 27651 AN: 152138 Hom.: 2981 Cov.: 34 AF XY: 0.182 AC XY: 13569 AN XY: 74370

African (AFR) AF: 0.0745 AC: 3098 AN: 41558

American (AMR) AF: 0.162 AC: 2483 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 800 AN: 3468

East Asian (EAS) AF: 0.436 AC: 2241 AN: 5144

South Asian (SAS) AF: 0.237 AC: 1142 AN: 4822

European-Finnish (FIN) AF: 0.237 AC: 2513 AN: 10582

Middle Eastern (MID) AF: 0.277 AC: 81 AN: 292

European-Non Finnish (NFE) AF: 0.215 AC: 14592 AN: 67952

Other (OTH) AF: 0.202 AC: 426 AN: 2114

Alfa AF: 0.206 Hom.: 9770

Bravo AF: 0.174

Asia WGS AF: 0.295 AC: 1027 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.45
PhyloP100		-1.2
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

Other links and lift over

dbSNP: rs11701058; hg19: chr21-47776382;