rs1298406367

Variant names:

• chr8-17937159-C-A
• NM_006197.4:c.122C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-17937159-C-A
• chr8-17937159-C-G
• chr8-17937159-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006197.4(PCM1):​c.122C>A​(p.Ala41Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PCM1 NM_006197.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.85

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCM1	NM_006197.4	c.122C>A	p.Ala41Glu	missense_variant	Exon 4 of 39	ENST00000325083.13	NP_006188.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCM1	ENST00000325083.13	c.122C>A	p.Ala41Glu	missense_variant	Exon 4 of 39	1	NM_006197.4	ENSP00000327077.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1418114 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 701442

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	.;.;T;.;T;.;.
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	.;D;D;D;D;.;.
M_CAP	Benign	0.066	D
MetaRNN	Uncertain	0.47	T;T;T;T;T;T;T
MetaSVM	Benign	-0.86	T
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-2.3	N;.;D;D;D;N;N
REVEL	Uncertain	0.38
Sift	Uncertain	0.0020	D;.;D;D;D;D;D
Sift4G	Uncertain	0.0060	D;D;D;D;D;D;D
Polyphen		1.0	.;.;D;.;.;.;.
Vest4		0.60
MutPred		0.12		Gain of ubiquitination at K39 (P = 0.0268);Gain of ubiquitination at K39 (P = 0.0268);Gain of ubiquitination at K39 (P = 0.0268);Gain of ubiquitination at K39 (P = 0.0268);Gain of ubiquitination at K39 (P = 0.0268);Gain of ubiquitination at K39 (P = 0.0268);Gain of ubiquitination at K39 (P = 0.0268);
MVP		0.74
ClinPred		0.84	D
GERP RS		5.6
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-17794668;