Variant 17-6445252-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_019013.3(PIMREG):c.142A>G(p.Arg48Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

PIMREG
NM_019013.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.99

Variant links:

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]

PIMREG links:

LOC107985017 (HGNC:):

LOC107985017 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.778

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIMREG	NM_019013.3 linkuse as main transcript	c.142A>G	p.Arg48Gly	missense_variant	2/6	ENST00000572447.6	NP_061886.2	Q9BSJ6-2A0A0S2Z5C7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIMREG	ENST00000572447.6 linkuse as main transcript	c.142A>G	p.Arg48Gly	missense_variant	2/6	1	NM_019013.3	ENSP00000459235.1		Q9BSJ6-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251096

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135786

show subpopulations

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 SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461660

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727120

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 10, 2024

The c.142A>G (p.R48G) alteration is located in exon 2 (coding exon 1) of the FAM64A gene. This alteration results from a A to G substitution at nucleotide position 142, causing the arginine (R) at amino acid position 48 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Uncertain

0.070

BayesDel_noAF

Uncertain

0.060

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

.;T;T;T;T;.

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Benign

0.63

LIST_S2

Uncertain

0.90

.;D;.;D;D;D

M_CAP

Benign

0.042

MetaRNN

Pathogenic

0.78

D;D;D;D;D;D

MetaSVM

Benign

-0.81

PrimateAI

Benign

0.48

PROVEAN

Pathogenic

-4.6

.;D;.;.;.;.

REVEL

Uncertain

0.35

Sift

Benign

0.092

.;T;.;.;.;.

Sift4G

Pathogenic

0.0

D;D;D;D;D;D

Polyphen

0.99

D;D;.;.;.;D

Vest4

0.64

MutPred

0.79

Loss of MoRF binding (P = 0.0159);Loss of MoRF binding (P = 0.0159);Loss of MoRF binding (P = 0.0159);Loss of MoRF binding (P = 0.0159);Loss of MoRF binding (P = 0.0159);Loss of MoRF binding (P = 0.0159);

MVP

0.68

MPC

0.68

ClinPred

0.87

GERP RS

2.7

Varity_R

0.33

gMVP

0.23

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over