rs2299587

chr8-17943260-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006197.4(PCM1):c.783+3399T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 149,602 control chromosomes in the GnomAD database, including 17,396 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 0.45 (17396 hom., cov: 27)
• Consequence: PCM1 NM_006197.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

Genes affected

PCM1 (HGNC:8727): (pericentriolar material 1) The protein encoded by this gene is a component of centriolar satellites, which are electron dense granules scattered around centrosomes. Inhibition studies show that this protein is essential for the correct localization of several centrosomal proteins, and for anchoring microtubules to the centrosome. Chromosomal aberrations involving this gene are associated with papillary thyroid carcinomas and a variety of hematological malignancies, including atypical chronic myeloid leukemia and T-cell lymphoma. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCM1	NM_006197.4	c.783+3399T>G		intron_variant		ENST00000325083.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCM1	ENST00000325083.13	c.783+3399T>G		intron_variant		1	NM_006197.4	P2

Frequencies

GnomAD3 genomes AF: 0.449 AC: 67057 AN: 149496 Hom.: 17399 Cov.: 27

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.581

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.470

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

GnomAD4 genome AF: 0.448 AC: 67051 AN: 149602 Hom.: 17396 Cov.: 27 AF XY: 0.441 AC XY: 32212 AN XY: 72980

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.483

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.365

Gnomad4 FIN AF: 0.588

Gnomad4 NFE AF: 0.608

Gnomad4 OTH AF: 0.471

Alfa AF: 0.580 Hom.: 35648

Asia WGS AF: 0.292 AC: 1012 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.54
Dann	Benign	0.38

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: rs2299587; hg19: chr8-17800769;