21-46352554-C-T

Variant names:

• chr21-46352554-C-T
• rs11702684
• NM_006031.6:c.1457-550C>T

Variant summary

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

The NM_006031.6(PCNT):​c.1457-550C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0927 in 152,186 control chromosomes in the GnomAD database, including 899 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 0.093 (899 hom., cov: 33)
• Consequence: PCNT NM_006031.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200
• Publications: 4 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: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.314 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCNT	NM_006031.6	MANE Select	c.1457-550C>T		intron	N/A	NP_006022.3
	PCNT	NM_001315529.2		c.1103-550C>T		intron	N/A	NP_001302458.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCNT	ENST00000359568.10	TSL:1 MANE Select	c.1457-550C>T		intron	N/A	ENSP00000352572.5
	PCNT	ENST00000480896.5	TSL:1	c.1103-550C>T		intron	N/A	ENSP00000511989.1
	PCNT	ENST00000695558.1		c.1457-550C>T		intron	N/A	ENSP00000512015.1

Frequencies

GnomAD3 genomes AF: 0.0928 AC: 14109 AN: 152068 Hom.: 901 Cov.: 33

Gnomad AFR AF: 0.0411

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.0597

Gnomad ASJ AF: 0.0968

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0957

Gnomad OTH AF: 0.0951

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

GnomAD4 genome AF: 0.0927 AC: 14107 AN: 152186 Hom.: 899 Cov.: 33 AF XY: 0.0966 AC XY: 7186 AN XY: 74388

African (AFR) AF: 0.0411 AC: 1705 AN: 41534

American (AMR) AF: 0.0596 AC: 911 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0968 AC: 336 AN: 3472

East Asian (EAS) AF: 0.327 AC: 1683 AN: 5144

South Asian (SAS) AF: 0.145 AC: 699 AN: 4816

European-Finnish (FIN) AF: 0.178 AC: 1890 AN: 10592

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0957 AC: 6511 AN: 68012

Other (OTH) AF: 0.0941 AC: 199 AN: 2114

Alfa AF: 0.0860 Hom.: 1230

Bravo AF: 0.0831

Asia WGS AF: 0.199 AC: 692 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.2
DANN	Benign	0.48
PhyloP100		-0.0020
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: rs11702684; hg19: chr21-47772468;