Genetic Variant PCM1:c.-22-5C>T (chr8-17935584-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006197.4(PCM1):c.-22-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0469 in 980,066 control chromosomes in the GnomAD database, including 1,752 homozygotes. 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: 𝑓 0.065 ( 456 hom., cov: 32)

Exomes 𝑓: 0.044 ( 1296 hom. )

Consequence

PCM1
NM_006197.4 splice_region, intron

Scores

Splicing: ADA: 0.00001375

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.586

Publications

10 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCM1	NM_006197.4 link	c.-22-5C>T		splice_region_variant, intron_variant	Intron 2 of 38	ENST00000325083.13	NP_006188.4	Q15154A2RUU9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCM1	ENST00000325083.13 link	c.-22-5C>T		splice_region_variant, intron_variant	Intron 2 of 38	1	NM_006197.4	ENSP00000327077.8		Q15154

Frequencies

GnomAD3 genomes

AF:

0.0650

AC:

9888

AN:

152044

Hom.:

456

Cov.:

show subpopulations

Gnomad AFR

AF:

0.115

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.102

Gnomad ASJ

AF:

0.0942

Gnomad EAS

AF:

0.0655

Gnomad SAS

AF:

0.0600

Gnomad FIN

AF:

0.0620

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0269

Gnomad OTH

AF:

0.0618

GnomAD2 exomes

AF:

0.0617

AC:

14020

AN:

227216

AF XY:

0.0587

show subpopulations

Gnomad AFR exome

AF:

0.116

Gnomad AMR exome

AF:

0.141

Gnomad ASJ exome

AF:

0.0994

Gnomad EAS exome

AF:

0.0654

Gnomad FIN exome

AF:

0.0587

Gnomad NFE exome

AF:

0.0271

Gnomad OTH exome

AF:

0.0540

GnomAD4 exome

AF:

0.0435

AC:

36036

AN:

827904

Hom.:

1296

Cov.:

AF XY:

0.0437

AC XY:

18989

AN XY:

434418

show subpopulations

African (AFR)

AF:

0.112

AC:

2396

AN:

21474

American (AMR)

AF:

0.137

AC:

5616

AN:

40988

Ashkenazi Jewish (ASJ)

AF:

0.0969

AC:

2107

AN:

21744

East Asian (EAS)

AF:

0.0576

AC:

2116

AN:

36708

South Asian (SAS)

AF:

0.0653

AC:

4614

AN:

70620

European-Finnish (FIN)

AF:

0.0533

AC:

2801

AN:

52566

Middle Eastern (MID)

AF:

0.0731

AC:

329

AN:

4500

European-Non Finnish (NFE)

AF:

0.0263

AC:

14208

AN:

539692

Other (OTH)

AF:

0.0467

AC:

1849

AN:

39612

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1669

3338

5006

6675

8344

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0650

AC:

9895

AN:

152162

Hom.:

456

Cov.:

AF XY:

0.0678

AC XY:

5039

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.115

AC:

4756

AN:

41506

American (AMR)

AF:

0.101

AC:

1549

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0942

AC:

327

AN:

3472

East Asian (EAS)

AF:

0.0653

AC:

338

AN:

5180

South Asian (SAS)

AF:

0.0598

AC:

289

AN:

4830

European-Finnish (FIN)

AF:

0.0620

AC:

657

AN:

10592

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0269

AC:

1827

AN:

67990

Other (OTH)

AF:

0.0611

AC:

129

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

477

954

1430

1907

2384

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0421

Hom.:

298

Bravo

AF:

0.0700

Asia WGS

AF:

0.0460

AC:

160

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

8.7

(source)

DANN

Benign

0.41

PhyloP100

0.59

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000014

dbscSNV1_RF

Benign

0.0

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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8-17935584-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over