8-17937364-C-G

Variant names:

• chr8-17937364-C-G
• rs201776854
• NM_006197.4:c.327C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006197.4(PCM1):​c.327C>G​(p.Phe109Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000269 in 1,596,552 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00032 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00026 (1 hom.)
• Consequence: PCM1 NM_006197.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.13
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008425415).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCM1	NM_006197.4	MANE Select	c.327C>G	p.Phe109Leu	missense	Exon 4 of 39	NP_006188.4
	PCM1	NM_001352632.2		c.327C>G	p.Phe109Leu	missense	Exon 4 of 40	NP_001339561.2
	PCM1	NM_001352650.2		c.327C>G	p.Phe109Leu	missense	Exon 6 of 42	NP_001339579.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCM1	ENST00000325083.13	TSL:1 MANE Select	c.327C>G	p.Phe109Leu	missense	Exon 4 of 39	ENSP00000327077.8	Q15154-1
	PCM1	ENST00000519253.5	TSL:1	c.327C>G	p.Phe109Leu	missense	Exon 4 of 39	ENSP00000431099.1	A0A5H1ZRS1
	PCM1	ENST00000524226.5	TSL:1	c.327C>G	p.Phe109Leu	missense	Exon 3 of 35	ENSP00000430521.1	A0A4W8VX11

Frequencies

GnomAD3 genomes AF: 0.000322 AC: 49 AN: 152082 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.0110

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.000463 AC: 104 AN: 224436 AF XY: 0.000512

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000989

Gnomad ASJ exome AF: 0.00912

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000983

Gnomad OTH exome AF: 0.000721

GnomAD4 exome AF: 0.000263 AC: 380 AN: 1444470 Hom.: 1 Cov.: 29 AF XY: 0.000283 AC XY: 203 AN XY: 716844

African (AFR) AF: 0.00 AC: 0 AN: 32932

American (AMR) AF: 0.0000957 AC: 4 AN: 41808

Ashkenazi Jewish (ASJ) AF: 0.00946 AC: 244 AN: 25798

East Asian (EAS) AF: 0.00 AC: 0 AN: 39290

South Asian (SAS) AF: 0.00 AC: 0 AN: 81502

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52938

Middle Eastern (MID) AF: 0.000522 AC: 3 AN: 5746

European-Non Finnish (NFE) AF: 0.0000742 AC: 82 AN: 1104574

Other (OTH) AF: 0.000785 AC: 47 AN: 59882

GnomAD4 genome AF: 0.000322 AC: 49 AN: 152082 Hom.: 1 Cov.: 32 AF XY: 0.000283 AC XY: 21 AN XY: 74288

African (AFR) AF: 0.00 AC: 0 AN: 41416

American (AMR) AF: 0.0000655 AC: 1 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0110 AC: 38 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68012

Other (OTH) AF: 0.000480 AC: 1 AN: 2082

Alfa AF: 0.000839 Hom.: 162

Bravo AF: 0.000283

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000607 AC: 5

ExAC AF: 0.000340 AC: 41

Asia WGS AF: 0.000577 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.0084	T
MetaSVM	Benign	-0.95	T
PhyloP100		4.1
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.20
Sift	Uncertain	0.0040	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.93
MutPred		0.25		Gain of phosphorylation at S110 (P = 0.1286)
MVP		0.51
ClinPred		0.12	T
GERP RS		5.8
gMVP		0.26
Mutation Taster		=30/70	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs201776854; hg19: chr8-17794873;