rs2299587

Variant names:

• chr8-17943260-T-G
• rs2299587
• NM_006197.4:c.783+3399T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PCM1	NM_006197.4	c.783+3399T>G		intron_variant	Intron 6 of 38	ENST00000325083.13	NP_006188.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCM1	ENST00000325083.13	c.783+3399T>G		intron_variant	Intron 6 of 38	1	NM_006197.4	ENSP00000327077.8

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

African (AFR) AF: 0.222 AC: 9124 AN: 41064

American (AMR) AF: 0.369 AC: 5556 AN: 15050

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 1666 AN: 3452

East Asian (EAS) AF: 0.142 AC: 724 AN: 5108

South Asian (SAS) AF: 0.365 AC: 1732 AN: 4748

European-Finnish (FIN) AF: 0.588 AC: 5773 AN: 9820

Middle Eastern (MID) AF: 0.583 AC: 168 AN: 288

European-Non Finnish (NFE) AF: 0.608 AC: 40792 AN: 67112

Other (OTH) AF: 0.471 AC: 972 AN: 2062

Alfa AF: 0.546 Hom.: 55638

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
PhyloP100		-1.0
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: rs2299587; hg19: chr8-17800769;