NM_019013.3:c.*15-3A>C

Variant names:

• chr17-6450359-A-C
• rs7218283
• NM_019013.3:c.*15-3A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019013.3(PIMREG):​c.*15-3A>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.887 in 1,556,426 control chromosomes in the GnomAD database, including 613,023 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.90 (61851 hom., cov: 31)
  • Exomes 𝑓: 0.89 (551172 hom.)
• Consequence: PIMREG NM_019013.3 splice_region, intron
• Scores: Splicing: ADA: 0.0001555
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.170
• Publications: 16 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIMREG	NM_019013.3	MANE Select	c.*15-3A>C		splice_region intron	N/A	NP_061886.2
	PIMREG	NM_001195228.2		c.687-3A>C		splice_region intron	N/A	NP_001182157.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIMREG	ENST00000572447.6	TSL:1 MANE Select	c.*15-3A>C		splice_region intron	N/A	ENSP00000459235.1
	PIMREG	ENST00000250056.12	TSL:1	c.687-3A>C		splice_region intron	N/A	ENSP00000250056.8
	PIMREG	ENST00000571572.2	TSL:2	c.*301A>C		3_prime_UTR	Exon 3 of 3	ENSP00000459860.2

Frequencies

GnomAD3 genomes AF: 0.901 AC: 136905 AN: 152024 Hom.: 61804 Cov.: 31

Gnomad AFR AF: 0.950

Gnomad AMI AF: 0.897

Gnomad AMR AF: 0.883

Gnomad ASJ AF: 0.879

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.866

Gnomad FIN AF: 0.863

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.887

Gnomad OTH AF: 0.899

GnomAD2 exomes AF: 0.877 AC: 151189 AN: 172434 AF XY: 0.876

Gnomad AFR exome AF: 0.950

Gnomad AMR exome AF: 0.861

Gnomad ASJ exome AF: 0.880

Gnomad EAS exome AF: 0.847

Gnomad FIN exome AF: 0.863

Gnomad NFE exome AF: 0.885

Gnomad OTH exome AF: 0.877

GnomAD4 exome AF: 0.886 AC: 1243593 AN: 1404284 Hom.: 551172 Cov.: 37 AF XY: 0.885 AC XY: 615224 AN XY: 695048

African (AFR) AF: 0.951 AC: 30960 AN: 32566

American (AMR) AF: 0.861 AC: 32725 AN: 38016

Ashkenazi Jewish (ASJ) AF: 0.882 AC: 22412 AN: 25408

East Asian (EAS) AF: 0.879 AC: 33107 AN: 37682

South Asian (SAS) AF: 0.861 AC: 69493 AN: 80756

European-Finnish (FIN) AF: 0.862 AC: 30591 AN: 35478

Middle Eastern (MID) AF: 0.909 AC: 5193 AN: 5714

European-Non Finnish (NFE) AF: 0.887 AC: 967112 AN: 1089774

Other (OTH) AF: 0.883 AC: 52000 AN: 58890

GnomAD4 genome AF: 0.901 AC: 137009 AN: 152142 Hom.: 61851 Cov.: 31 AF XY: 0.900 AC XY: 66950 AN XY: 74384

African (AFR) AF: 0.950 AC: 39448 AN: 41524

American (AMR) AF: 0.883 AC: 13521 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.879 AC: 3051 AN: 3472

East Asian (EAS) AF: 0.854 AC: 4403 AN: 5154

South Asian (SAS) AF: 0.865 AC: 4160 AN: 4812

European-Finnish (FIN) AF: 0.863 AC: 9128 AN: 10576

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.887 AC: 60317 AN: 67984

Other (OTH) AF: 0.898 AC: 1894 AN: 2108

Alfa AF: 0.889 Hom.: 68396

Bravo AF: 0.903

Asia WGS AF: 0.857 AC: 2979 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.5
DANN	Benign	0.78
PhyloP100		0.17
Mutation Taster		=45/55	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00016
dbscSNV1_RF	Benign	0.096
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: rs7218283; hg19: chr17-6353679; COSMIC: COSV51471978; COSMIC: COSV51471978;