rs1268444003

Variant names:

• chr8-17935694-G-A
• rs1268444003
• NM_006197.4:c.84G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-17935694-G-A
• chr8-17935694-G-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_006197.4(PCM1):​c.84G>A​(p.Arg28Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP7: Synonymous conserved (PhyloP=0.264 with no splicing effect.

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.84G>A	p.Arg28Arg	synonymous	Exon 3 of 39	NP_006188.4
	PCM1	NM_001352632.2		c.84G>A	p.Arg28Arg	synonymous	Exon 3 of 40	NP_001339561.2
	PCM1	NM_001352650.2		c.84G>A	p.Arg28Arg	synonymous	Exon 5 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.84G>A	p.Arg28Arg	synonymous	Exon 3 of 39	ENSP00000327077.8	Q15154-1
	PCM1	ENST00000519253.5	TSL:1	c.84G>A	p.Arg28Arg	synonymous	Exon 3 of 39	ENSP00000431099.1	A0A5H1ZRS1
	PCM1	ENST00000524226.5	TSL:1	c.84G>A	p.Arg28Arg	synonymous	Exon 2 of 35	ENSP00000430521.1	A0A4W8VX11

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1270006 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 641150

African (AFR) AF: 0.00 AC: 0 AN: 29742

American (AMR) AF: 0.00 AC: 0 AN: 44312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24908

East Asian (EAS) AF: 0.00 AC: 0 AN: 38788

South Asian (SAS) AF: 0.00 AC: 0 AN: 82092

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5392

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 937460

Other (OTH) AF: 0.00 AC: 0 AN: 54036

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	6.6
DANN	Benign	0.68
PhyloP100		0.26
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs1268444003; hg19: chr8-17793203;