8-17935705-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006197.4(PCM1):​c.95T>G​(p.Met32Arg) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

PCM1
NM_006197.4 missense, splice_region

Scores

1
8
9
Splicing: ADA: 0.7684
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.11
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.25119025).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PCM1NM_006197.4 linkuse as main transcriptc.95T>G p.Met32Arg missense_variant, splice_region_variant 3/39 ENST00000325083.13 NP_006188.4 Q15154A2RUU9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PCM1ENST00000325083.13 linkuse as main transcriptc.95T>G p.Met32Arg missense_variant, splice_region_variant 3/391 NM_006197.4 ENSP00000327077.8 Q15154

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
17
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsJun 26, 2024The c.95T>G (p.M32R) alteration is located in exon 3 (coding exon 1) of the PCM1 gene. This alteration results from a T to G substitution at nucleotide position 95, causing the methionine (M) at amino acid position 32 to be replaced by an arginine (R). 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
Benign
0.15
BayesDel_addAF
Uncertain
0.045
T
BayesDel_noAF
Benign
-0.17
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.11
.;.;T;.;T;.;.
Eigen
Uncertain
0.41
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.86
.;D;D;D;D;.;.
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.25
T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-2.3
N;.;D;D;D;N;N
REVEL
Benign
0.16
Sift
Uncertain
0.0070
D;.;D;D;D;D;D
Sift4G
Uncertain
0.024
D;D;T;D;D;D;D
Polyphen
0.98
.;.;D;.;.;.;.
Vest4
0.70
MutPred
0.32
Loss of stability (P = 0.0029);Loss of stability (P = 0.0029);Loss of stability (P = 0.0029);Loss of stability (P = 0.0029);Loss of stability (P = 0.0029);Loss of stability (P = 0.0029);Loss of stability (P = 0.0029);
MVP
0.47
ClinPred
0.86
D
GERP RS
5.2
gMVP
0.36

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.77
dbscSNV1_RF
Benign
0.63
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-17793214; API