17-6447515-T-G

Variant names:

• chr17-6447515-T-G
• rs1034992973
• NM_019013.3:c.347T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_019013.3(PIMREG):​c.347T>G​(p.Val116Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V116A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PIMREG NM_019013.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3386446).

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.347T>G	p.Val116Gly	missense	Exon 3 of 6	NP_061886.2	Q9BSJ6-2
	PIMREG	NM_001195228.2		c.347T>G	p.Val116Gly	missense	Exon 3 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.347T>G	p.Val116Gly	missense	Exon 3 of 6	ENSP00000459235.1	Q9BSJ6-2
	PIMREG	ENST00000250056.12	TSL:1	c.347T>G	p.Val116Gly	missense	Exon 3 of 5	ENSP00000250056.8	Q9BSJ6-1
	PIMREG	ENST00000572595.6	TSL:3	c.440T>G	p.Val147Gly	missense	Exon 4 of 6	ENSP00000458584.2	I3L156

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1461680 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727142

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111892

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.56	T
PhyloP100		1.4
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-4.0	D
REVEL	Uncertain	0.38
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.37
MutPred		0.57		Loss of methylation at K117 (P = 0.0421)
MVP		0.73
MPC		0.37
ClinPred		0.93	D
GERP RS		3.4
PromoterAI		0.020	Neutral
Varity_R		0.67
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1034992973; hg19: chr17-6350835;