Variant 8-17938792-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006197.4(PCM1):c.395G>T(p.Arg132Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,142 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PCM1
NM_006197.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.90

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCM1	NM_006197.4 linkuse as main transcript	c.395G>T	p.Arg132Leu	missense_variant	5/39	ENST00000325083.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCM1	ENST00000325083.13 linkuse as main transcript	c.395G>T	p.Arg132Leu	missense_variant	5/39	1	NM_006197.4	P2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460142

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726472

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:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jul 05, 2023

The c.395G>T (p.R132L) alteration is located in exon 5 (coding exon 3) of the PCM1 gene. This alteration results from a G to T substitution at nucleotide position 395, causing the arginine (R) at amino acid position 132 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

0.83

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.12

Cadd

Pathogenic

Dann

Uncertain

1.0

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.87

FATHMM_MKL

Pathogenic

1.0

M_CAP

Benign

0.047

MetaRNN

Uncertain

0.52

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

MetaSVM

Benign

-0.95

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-3.8

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

REVEL

Uncertain

0.45

Sift

Pathogenic

0.0

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

Sift4G

Pathogenic

0.0

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

Polyphen

1.0

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

Vest4

0.87

MutPred

0.25

Loss of MoRF binding (P = 0.0206);Loss of MoRF binding (P = 0.0206);Loss of MoRF binding (P = 0.0206);Loss of MoRF binding (P = 0.0206);Loss of MoRF binding (P = 0.0206);Loss of MoRF binding (P = 0.0206);Loss of MoRF binding (P = 0.0206);

MVP

0.72

ClinPred

0.99

GERP RS

5.8

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over