rs12746

Variant names:

• chr17-6451011-G-A
• rs12746
• NM_019013.3:c.*664G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PIMREG	NM_019013.3	c.*664G>A		3_prime_UTR_variant	Exon 6 of 6	ENST00000572447.6	NP_061886.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIMREG	ENST00000572447.6	c.*664G>A		3_prime_UTR_variant	Exon 6 of 6	1	NM_019013.3	ENSP00000459235.1
PIMREG	ENST00000250056.12	c.*589G>A		3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000250056.8
PIMREG	ENST00000572595.6	c.*589G>A		3_prime_UTR_variant	Exon 6 of 6	3		ENSP00000458584.2

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

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AF: 0.500 AC: 3 AN: 6

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.667 AC: 4 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.705 AC: 31 AN: 44

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.679 AC: 28161 AN: 41494

American (AMR) AF: 0.656 AC: 10022 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 2088 AN: 3470

East Asian (EAS) AF: 0.720 AC: 3727 AN: 5178

South Asian (SAS) AF: 0.704 AC: 3398 AN: 4828

European-Finnish (FIN) AF: 0.676 AC: 7146 AN: 10574

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.662 AC: 45013 AN: 67984

Other (OTH) AF: 0.635 AC: 1338 AN: 2108

Alfa AF: 0.653 Hom.: 38116

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
PhyloP100		0.088
Mutation Taster		=100/0	polymorphism (auto)

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: rs12746; hg19: chr17-6354331;