8-18021218-T-C

Position:

• chr8-18021218-T-C

Variant summary

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

The NM_006197.4(PCM1):​c.5842-4143T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 152,042 control chromosomes in the GnomAD database, including 9,058 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 0.30 (9058 hom., cov: 32)
• Consequence: PCM1 NM_006197.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214

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]

PCM1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCM1	NM_006197.4	c.5842-4143T>C		intron_variant		ENST00000325083.13	NP_006188.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCM1	ENST00000325083.13	c.5842-4143T>C		intron_variant		1	NM_006197.4	ENSP00000327077.8

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46304 AN: 151926 Hom.: 9039 Cov.: 32

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.305 AC: 46362 AN: 152042 Hom.: 9058 Cov.: 32 AF XY: 0.306 AC XY: 22770 AN XY: 74306

Gnomad4 AFR AF: 0.548

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.419

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.269

Alfa AF: 0.164 Hom.: 540

Bravo AF: 0.316

Asia WGS AF: 0.282 AC: 983 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.7
DANN	Benign	0.67

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: rs208024; hg19: chr8-17878727;