Variant 8-17937344-C-G 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.307C>G(p.Leu103Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,452,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PCM1
NM_006197.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.02

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:

PCM1 (HGNC:):

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=0.34239346).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCM1	NM_006197.4 linkuse as main transcript	c.307C>G	p.Leu103Val	missense_variant	4/39	ENST00000325083.13	NP_006188.4	Q15154A2RUU9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCM1	ENST00000325083.13 linkuse as main transcript	c.307C>G	p.Leu103Val	missense_variant	4/39	1	NM_006197.4	ENSP00000327077.8		Q15154

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000422

AC:

AN:

236712

Hom.:

AF XY:

0.00

AC XY:

AN XY:

127896

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000578

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1452818

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

721770

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

AC:

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 08, 2024

The c.307C>G (p.L103V) 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 307, causing the leucine (L) at amino acid position 103 to be replaced by a valine (V). 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

0.45

BayesDel_addAF

Benign

-0.030

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

.;.;T;.;T;.;.

Eigen

Uncertain

0.65

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

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

M_CAP

Benign

0.027

MetaRNN

Benign

0.34

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

MetaSVM

Benign

-0.73

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.8

N;.;D;D;N;N;N

REVEL

Benign

0.21

Sift

Pathogenic

0.0

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

Sift4G

Pathogenic

0.0

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

Polyphen

0.99

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

Vest4

0.86

MutPred

0.19

Gain of methylation at K104 (P = 0.0319);Gain of methylation at K104 (P = 0.0319);Gain of methylation at K104 (P = 0.0319);Gain of methylation at K104 (P = 0.0319);Gain of methylation at K104 (P = 0.0319);Gain of methylation at K104 (P = 0.0319);Gain of methylation at K104 (P = 0.0319);

MVP

0.62

ClinPred

0.75

GERP RS

5.8

gMVP

0.37

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

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