Variant 8-17935584-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006197.4(PCM1):c.-22-5C>T variant causes a splice region, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001375

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.586

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 Benign. Variant got -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/exons	MANE	Protein	UniProt
PCM1	NM_006197.4 linkuse as main transcript	c.-22-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000325083.13	NP_006188.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCM1	ENST00000325083.13 linkuse as main transcript	c.-22-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_006197.4	ENSP00000327077	P2

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

GnomAD3 exomes

AF:

0.0617

AC:

14020

AN:

227216

Hom.:

659

AF XY:

0.0587

AC XY:

7178

AN XY:

122378

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 SAS exome

AF:

0.0614

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

Gnomad4 AFR exome

AF:

0.112

Gnomad4 AMR exome

AF:

0.137

Gnomad4 ASJ exome

AF:

0.0969

Gnomad4 EAS exome

AF:

0.0576

Gnomad4 SAS exome

AF:

0.0653

Gnomad4 FIN exome

AF:

0.0533

Gnomad4 NFE exome

AF:

0.0263

Gnomad4 OTH exome

AF:

0.0467

GnomAD4 genome

AF:

0.0650

AC:

9895

AN:

152162

Hom.:

456

Cov.:

AF XY:

0.0678

AC XY:

5039

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.115

Gnomad4 AMR

AF:

0.101

Gnomad4 ASJ

AF:

0.0942

Gnomad4 EAS

AF:

0.0653

Gnomad4 SAS

AF:

0.0598

Gnomad4 FIN

AF:

0.0620

Gnomad4 NFE

AF:

0.0269

Gnomad4 OTH

AF:

0.0611

Alfa

AF:

0.0373

Hom.:

179

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

DANN

Benign

0.41

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over