rs12746

Positions:

• chr17-6451011-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019013.3(PIMREG):​c.*664G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 152,194 control chromosomes in the GnomAD database, including 33,934 homozygotes. 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: 𝑓 0.67 (33920 hom., cov: 34)
  • Exomes 𝑓: 0.64 (14 hom.)
• Consequence: PIMREG NM_019013.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0880

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIMREG	NM_019013.3	c.*664G>A		3_prime_UTR_variant	6/6	ENST00000572447.6	NP_061886.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIMREG	ENST00000572447.6	c.*664G>A		3_prime_UTR_variant	6/6	1	NM_019013.3	ENSP00000459235	P2
PIMREG	ENST00000250056.12	c.*589G>A		3_prime_UTR_variant	5/5	1		ENSP00000250056	A2
PIMREG	ENST00000572595.6	c.*589G>A		3_prime_UTR_variant	6/6	3		ENSP00000458584

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101529 AN: 152012 Hom.: 33885 Cov.: 34

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.656

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.705

Gnomad FIN AF: 0.676

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.632

GnomAD4 exome AF: 0.641 AC: 41 AN: 64 Hom.: 14 Cov.: 0 AF XY: 0.567 AC XY: 17 AN XY: 30

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.667

Gnomad4 NFE exome AF: 0.705

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.668 AC: 101618 AN: 152130 Hom.: 33920 Cov.: 34 AF XY: 0.671 AC XY: 49905 AN XY: 74368

Gnomad4 AFR AF: 0.679

Gnomad4 AMR AF: 0.656

Gnomad4 ASJ AF: 0.602

Gnomad4 EAS AF: 0.720

Gnomad4 SAS AF: 0.704

Gnomad4 FIN AF: 0.676

Gnomad4 NFE AF: 0.662

Gnomad4 OTH AF: 0.635

Alfa AF: 0.652 Hom.: 31297

Bravo AF: 0.662

Asia WGS AF: 0.697 AC: 2421 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	9.0
DANN	Benign	0.87

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

LitVar

Other links and lift over

dbSNP: rs12746; hg19: chr17-6354331;