Variant 8-17937364-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006197.4(PCM1):c.327C>G(p.Phe109Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000269 in 1,596,552 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00026 ( 1 hom. )

Consequence

PCM1
NM_006197.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.13

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008425415).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCM1	NM_006197.4 linkuse as main transcript	c.327C>G	p.Phe109Leu	missense_variant	4/39	ENST00000325083.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCM1	ENST00000325083.13 linkuse as main transcript	c.327C>G	p.Phe109Leu	missense_variant	4/39	1	NM_006197.4	P2

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.0110

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.000463

AC:

104

AN:

224436

Hom.:

AF XY:

0.000512

AC XY:

AN XY:

121110

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000989

Gnomad ASJ exome

AF:

0.00912

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000983

Gnomad OTH exome

AF:

0.000721

GnomAD4 exome

AF:

0.000263

AC:

380

AN:

1444470

Hom.:

Cov.:

AF XY:

0.000283

AC XY:

203

AN XY:

716844

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000957

Gnomad4 ASJ exome

AF:

0.00946

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000742

Gnomad4 OTH exome

AF:

0.000785

GnomAD4 genome

AF:

0.000322

AC:

AN:

152082

Hom.:

Cov.:

AF XY:

0.000283

AC XY:

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.0110

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.000480

Alfa

AF:

0.000849

Hom.:

Bravo

AF:

0.000283

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000607

AC:

ExAC

AF:

0.000340

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 15, 2021

The c.327C>G (p.F109L) alteration is located in exon 4 (coding exon 2) of the PCM1 gene. This alteration results from a C to G substitution at nucleotide position 327, causing the phenylalanine (F) at amino acid position 109 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Benign

-0.028

BayesDel_noAF

Uncertain

-0.070

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Pathogenic

0.98

M_CAP

Benign

0.038

MetaRNN

Benign

0.0084

T;T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.88

PROVEAN

Uncertain

-3.7

D;.;D;D;D;D;D

REVEL

Benign

0.20

Sift

Uncertain

0.0040

D;.;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;T;D;D;D;D

Polyphen

0.99

.;.;D;.;.;.;.

Vest4

0.93

MutPred

0.25

Gain of phosphorylation at S110 (P = 0.1286);Gain of phosphorylation at S110 (P = 0.1286);Gain of phosphorylation at S110 (P = 0.1286);Gain of phosphorylation at S110 (P = 0.1286);Gain of phosphorylation at S110 (P = 0.1286);Gain of phosphorylation at S110 (P = 0.1286);Gain of phosphorylation at S110 (P = 0.1286);

MVP

0.51

ClinPred

0.12

GERP RS

5.8

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over