NM_006197.4:c.-22-5C>T

Variant names:

• chr8-17935584-C-T
• rs445422
• NM_006197.4:c.-22-5C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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

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: 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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCM1	NM_006197.4	MANE Select	c.-22-5C>T		splice_region intron	N/A	NP_006188.4
	PCM1	NM_001352632.2		c.-22-5C>T		splice_region intron	N/A	NP_001339561.2
	PCM1	NM_001352650.2		c.-22-5C>T		splice_region intron	N/A	NP_001339579.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCM1	ENST00000325083.13	TSL:1 MANE Select	c.-22-5C>T		splice_region intron	N/A	ENSP00000327077.8
	PCM1	ENST00000519253.5	TSL:1	c.-22-5C>T		splice_region intron	N/A	ENSP00000431099.1
	PCM1	ENST00000524226.5	TSL:1	c.-22-5C>T		splice_region intron	N/A	ENSP00000430521.1

Frequencies

GnomAD3 genomes AF: 0.0650 AC: 9888 AN: 152044 Hom.: 456 Cov.: 32

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

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.: 11 AF XY: 0.0437 AC XY: 18989 AN XY: 434418

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

GnomAD4 genome AF: 0.0650 AC: 9895 AN: 152162 Hom.: 456 Cov.: 32 AF XY: 0.0678 AC XY: 5039 AN XY: 74374

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: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0269 AC: 1827 AN: 67990

Other (OTH) AF: 0.0611 AC: 129 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.7
DANN	Benign	0.41
PhyloP100		0.59
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs445422; hg19: chr8-17793093; COSMIC: COSV61515365; COSMIC: COSV61515365;