8-17937377-C-A

Variant names:

• chr8-17937377-C-A
• rs1348160886
• NM_006197.4:c.340C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006197.4(PCM1):​c.340C>A​(p.Gln114Lys) 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. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q114E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PCM1 NM_006197.4 missense, splice_region
• Scores: Splicing: ADA: 0.9334
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.35
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28838593).

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.340C>A	p.Gln114Lys	missense splice_region	Exon 4 of 39	NP_006188.4
	PCM1	NM_001352632.2		c.340C>A	p.Gln114Lys	missense splice_region	Exon 4 of 40	NP_001339561.2
	PCM1	NM_001352650.2		c.340C>A	p.Gln114Lys	missense splice_region	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.340C>A	p.Gln114Lys	missense splice_region	Exon 4 of 39	ENSP00000327077.8	Q15154-1
	PCM1	ENST00000519253.5	TSL:1	c.340C>A	p.Gln114Lys	missense splice_region	Exon 4 of 39	ENSP00000431099.1	A0A5H1ZRS1
	PCM1	ENST00000524226.5	TSL:1	c.340C>A	p.Gln114Lys	missense splice_region	Exon 3 of 35	ENSP00000430521.1	A0A4W8VX11

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.037	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.1	T
PhyloP100		6.4
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.14
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.019	D
Polyphen		0.93	P
Vest4		0.52
MutPred		0.27		Gain of solvent accessibility (P = 0.0038)
MVP		0.52
ClinPred		0.74	D
GERP RS		5.8
gMVP		0.20
Mutation Taster		=63/37	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.93
dbscSNV1_RF	Pathogenic	0.77
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: rs1348160886; hg19: chr8-17794886;