8-17947015-C-T

Variant names:

• chr8-17947015-C-T
• rs13276297
• NM_006197.4:c.784-171C>T

Variant summary

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

The NM_006197.4(PCM1):​c.784-171C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0283 in 152,108 control chromosomes in the GnomAD database, including 96 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 0.028 (96 hom., cov: 31)
• Consequence: PCM1 NM_006197.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.192
• Publications: 3 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCM1	NM_006197.4	c.784-171C>T		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.784-171C>T		intron_variant	Intron 6 of 38	1	NM_006197.4	ENSP00000327077.8

Frequencies

GnomAD3 genomes AF: 0.0283 AC: 4299 AN: 151990 Hom.: 96 Cov.: 31

Gnomad AFR AF: 0.00906

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.0171

Gnomad ASJ AF: 0.0228

Gnomad EAS AF: 0.0791

Gnomad SAS AF: 0.0584

Gnomad FIN AF: 0.0133

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0381

Gnomad OTH AF: 0.0239

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

GnomAD4 genome AF: 0.0283 AC: 4308 AN: 152108 Hom.: 96 Cov.: 31 AF XY: 0.0276 AC XY: 2053 AN XY: 74352

African (AFR) AF: 0.00918 AC: 381 AN: 41506

American (AMR) AF: 0.0170 AC: 260 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0228 AC: 79 AN: 3466

East Asian (EAS) AF: 0.0791 AC: 409 AN: 5170

South Asian (SAS) AF: 0.0589 AC: 283 AN: 4806

European-Finnish (FIN) AF: 0.0133 AC: 141 AN: 10588

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0381 AC: 2588 AN: 67998

Other (OTH) AF: 0.0246 AC: 52 AN: 2114

Alfa AF: 0.0146 Hom.: 7

Bravo AF: 0.0269

Asia WGS AF: 0.0580 AC: 201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.0
DANN	Benign	0.70
PhyloP100		-0.19
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: rs13276297; hg19: chr8-17804524;