Variant 8-17939859-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006197.4(PCM1):c.781C>T(p.Leu261Phe) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000616 in 1,298,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

PCM1
NM_006197.4 missense, splice_region

Scores

Splicing: ADA: 0.01644

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.06

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2799151).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCM1	NM_006197.4 linkuse as main transcript	c.781C>T	p.Leu261Phe	missense_variant, splice_region_variant	6/39	ENST00000325083.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCM1	ENST00000325083.13 linkuse as main transcript	c.781C>T	p.Leu261Phe	missense_variant, splice_region_variant	6/39	1	NM_006197.4	P2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000140

AC:

AN:

143294

Hom.:

AF XY:

0.00

AC XY:

AN XY:

75760

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000344

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1298620

Hom.:

Cov.:

AF XY:

0.00000155

AC XY:

AN XY:

644548

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000601

Gnomad4 OTH exome

AF:

0.0000367

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000434

Hom.:

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

Jan 24, 2023

The c.781C>T (p.L261F) alteration is located in exon 6 (coding exon 4) of the PCM1 gene. This alteration results from a C to T substitution at nucleotide position 781, causing the leucine (L) at amino acid position 261 to be replaced by a phenylalanine (F). 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

Uncertain

0.38

BayesDel_addAF

Benign

-0.092

BayesDel_noAF

Benign

-0.26

Cadd

Benign

Dann

Uncertain

1.0

Eigen

Benign

-0.011

Eigen_PC

Benign

-0.074

FATHMM_MKL

Pathogenic

0.97

M_CAP

Benign

0.030

MetaRNN

Benign

0.28

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

MetaSVM

Benign

-0.94

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-2.2

N;N;D;D;D;N;N

REVEL

Benign

0.16

Sift

Uncertain

0.0080

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

Sift4G

Uncertain

0.010

D;D;D;D;D;D;D

Polyphen

0.88

.;.;P;.;.;.;.

Vest4

0.76

MutPred

0.21

Loss of ubiquitination at K259 (P = 0.0665);Loss of ubiquitination at K259 (P = 0.0665);Loss of ubiquitination at K259 (P = 0.0665);Loss of ubiquitination at K259 (P = 0.0665);Loss of ubiquitination at K259 (P = 0.0665);Loss of ubiquitination at K259 (P = 0.0665);Loss of ubiquitination at K259 (P = 0.0665);

MVP

0.54

ClinPred

0.51

GERP RS

3.4

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.016

dbscSNV1_RF

Benign

0.25

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

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