NM_019013.3:c.8C>T

Variant names:

• chr17-6445118-C-T
• NM_019013.3:c.8C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_019013.3(PIMREG):​c.8C>T​(p.Ser3Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,441,234 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PIMREG NM_019013.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.31
• Publications: 0 publications found

Genes affected

PIMREG (HGNC:25483): (PICALM interacting mitotic regulator) Predicted to be involved in cell division. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LOC107985017 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019013.3. 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
	PIMREG	NM_019013.3	MANE Select	c.8C>T	p.Ser3Phe	missense	Exon 2 of 6	NP_061886.2	Q9BSJ6-2
	PIMREG	NM_001195228.2		c.8C>T	p.Ser3Phe	missense	Exon 2 of 5	NP_001182157.1	Q9BSJ6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIMREG	ENST00000572447.6	TSL:1 MANE Select	c.8C>T	p.Ser3Phe	missense	Exon 2 of 6	ENSP00000459235.1	Q9BSJ6-2
	PIMREG	ENST00000250056.12	TSL:1	c.8C>T	p.Ser3Phe	missense	Exon 2 of 5	ENSP00000250056.8	Q9BSJ6-1
	PIMREG	ENST00000572595.6	TSL:3	c.8C>T	p.Ser3Phe	missense	Exon 2 of 6	ENSP00000458584.2	I3L156

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1441234 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 715610

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32342

American (AMR) AF: 0.00 AC: 0 AN: 40900

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24826

East Asian (EAS) AF: 0.00 AC: 0 AN: 39434

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84782

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52972

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5482

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101310

Other (OTH) AF: 0.00 AC: 0 AN: 59186

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

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	Uncertain	0.34
BayesDel_addAF	Benign	-0.0076	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-0.75	T
PhyloP100		2.3
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.98	D
Vest4		0.66
MutPred		0.53		Loss of phosphorylation at S3 (P = 0.0421)
MVP		0.68
MPC		0.62
ClinPred		0.99	D
GERP RS		3.7
Varity_R		0.48
gMVP		0.25

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

hg19: chr17-6348438;