Genetic Variant PCM1:p.Ala41Glu (chr8-17937159-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006197.4(PCM1):c.122C>A(p.Ala41Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A41V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PCM1
NM_006197.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.85

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006197.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PCM1	NM_006197.4	MANE Select	c.122C>A	p.Ala41Glu	missense	Exon 4 of 39	NP_006188.4
PCM1	NM_001352632.2		c.122C>A	p.Ala41Glu	missense	Exon 4 of 40	NP_001339561.2
PCM1	NM_001352650.2		c.122C>A	p.Ala41Glu	missense	Exon 6 of 42	NP_001339579.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PCM1	ENST00000325083.13	TSL:1 MANE Select	c.122C>A	p.Ala41Glu	missense	Exon 4 of 39	ENSP00000327077.8	Q15154-1
PCM1	ENST00000519253.5	TSL:1	c.122C>A	p.Ala41Glu	missense	Exon 4 of 39	ENSP00000431099.1	A0A5H1ZRS1
PCM1	ENST00000524226.5	TSL:1	c.122C>A	p.Ala41Glu	missense	Exon 3 of 35	ENSP00000430521.1	A0A4W8VX11

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1418114

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

701442

African (AFR)

AF:

0.00

AC:

AN:

32534

American (AMR)

AF:

0.00

AC:

AN:

37652

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25344

East Asian (EAS)

AF:

0.00

AC:

AN:

37998

South Asian (SAS)

AF:

0.00

AC:

AN:

80922

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51184

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5704

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1087892

Other (OTH)

AF:

0.00

AC:

AN:

58884

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.59

BayesDel_addAF

Pathogenic

0.16

BayesDel_noAF

Uncertain

0.0

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.066

MetaRNN

Uncertain

0.47

MetaSVM

Benign

-0.86

PhyloP100

7.9

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-2.3

REVEL

Uncertain

0.38

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.60

MutPred

0.12

Gain of ubiquitination at K39 (P = 0.0268)

MVP

0.74

ClinPred

0.84

GERP RS

5.6

gMVP

0.27

Mutation Taster

=15/85

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over