rs34478029

Variant names:

• chr8-17935675-A-C
• rs34478029
• NM_006197.4:c.65A>C

Your query was ambiguous. Multiple possible variants found:

• chr8-17935675-A-C
• chr8-17935675-A-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006197.4(PCM1):​c.65A>C​(p.Asn22Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000032 in 1,530,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N22S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: PCM1 NM_006197.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.388
• Publications: 3 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.02918002).

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.65A>C	p.Asn22Thr	missense	Exon 3 of 39	NP_006188.4
	PCM1	NM_001352632.2		c.65A>C	p.Asn22Thr	missense	Exon 3 of 40	NP_001339561.2
	PCM1	NM_001352650.2		c.65A>C	p.Asn22Thr	missense	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.65A>C	p.Asn22Thr	missense	Exon 3 of 39	ENSP00000327077.8	Q15154-1
	PCM1	ENST00000519253.5	TSL:1	c.65A>C	p.Asn22Thr	missense	Exon 3 of 39	ENSP00000431099.1	A0A5H1ZRS1
	PCM1	ENST00000524226.5	TSL:1	c.65A>C	p.Asn22Thr	missense	Exon 2 of 35	ENSP00000430521.1	A0A4W8VX11

Frequencies

GnomAD3 genomes AF: 0.000131 AC: 20 AN: 152182 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000484 AC: 12 AN: 247974 AF XY: 0.0000446

Gnomad AFR exome AF: 0.000649

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.0000203 AC: 28 AN: 1378574 Hom.: 0 Cov.: 22 AF XY: 0.0000116 AC XY: 8 AN XY: 690532

African (AFR) AF: 0.000723 AC: 23 AN: 31822

American (AMR) AF: 0.0000674 AC: 3 AN: 44510

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25578

East Asian (EAS) AF: 0.00 AC: 0 AN: 39284

South Asian (SAS) AF: 0.00 AC: 0 AN: 84376

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53344

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5608

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1036400

Other (OTH) AF: 0.0000347 AC: 2 AN: 57652

GnomAD4 genome AF: 0.000138 AC: 21 AN: 152300 Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8 AN XY: 74476

African (AFR) AF: 0.000457 AC: 19 AN: 41560

American (AMR) AF: 0.000131 AC: 2 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000164 Hom.: 0

Bravo AF: 0.000200

ESP6500AA AF: 0.000259 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000414 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	2.9
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.42
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.39
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.086
Sift	Uncertain	0.027	D
Sift4G	Benign	0.19	T
Polyphen		0.056	B
Vest4		0.29
MVP		0.26
ClinPred		0.032	T
GERP RS		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.12
Mutation Taster		=91/9	polymorphism

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: rs34478029; hg19: chr8-17793184;