chr17-6447611-C-T

Variant names:

• chr17-6447611-C-T
• rs1473119360
• NM_019013.3:c.443C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019013.3(PIMREG):​c.443C>T​(p.Pro148Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,714 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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. P148H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PIMREG NM_019013.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.201
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2432006).

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.443C>T	p.Pro148Leu	missense	Exon 3 of 6	NP_061886.2	Q9BSJ6-2
	PIMREG	NM_001195228.2		c.443C>T	p.Pro148Leu	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.443C>T	p.Pro148Leu	missense	Exon 3 of 6	ENSP00000459235.1	Q9BSJ6-2
	PIMREG	ENST00000250056.12	TSL:1	c.443C>T	p.Pro148Leu	missense	Exon 3 of 5	ENSP00000250056.8	Q9BSJ6-1
	PIMREG	ENST00000572595.6	TSL:3	c.536C>T	p.Pro179Leu	missense	Exon 4 of 6	ENSP00000458584.2	I3L156

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 250086 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000887

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461714 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727140

⚠️ 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: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111944

Other (OTH) AF: 0.00 AC: 0 AN: 60376

⚠️ 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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	7.3
DANN	Uncertain	1.0
DEOGEN2	Benign	0.094	T
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.92	T
PhyloP100		0.20
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.13
Sift	Benign	0.057	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.94	P
Vest4		0.25
MutPred		0.43		Loss of loop (P = 0.0022)
MVP		0.64
MPC		0.15
ClinPred		0.19	T
GERP RS		2.6
PromoterAI		0.0050	Neutral
Varity_R		0.017
gMVP		0.11

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: rs1473119360; hg19: chr17-6350931;