Variant 17-6445148-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_019013.3(PIMREG):c.38G>T(p.Arg13Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,456,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign 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: 0.000011 ( 0 hom. )

Consequence

PIMREG
NM_019013.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.19

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33775377).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIMREG	NM_019013.3 linkuse as main transcript	c.38G>T	p.Arg13Leu	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.38G>T	p.Arg13Leu	missense_variant	2/6	1	NM_019013.3	ENSP00000459235.1		Q9BSJ6-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000487

AC:

AN:

246606

Hom.:

AF XY:

0.0000225

AC XY:

AN XY:

133630

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000356

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1456850

Hom.:

Cov.:

AF XY:

0.00000966

AC XY:

AN XY:

724272

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000342

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000412

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

Nov 27, 2024

The c.38G>T (p.R13L) alteration is located in exon 2 (coding exon 1) of the FAM64A gene. This alteration results from a G to T substitution at nucleotide position 38, causing the arginine (R) at amino acid position 13 to be replaced by a leucine (L). 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

0.14

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.13

.;T;T;T;T;.

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.41

.;T;.;T;T;T

M_CAP

Benign

0.033

MetaRNN

Benign

0.34

T;T;T;T;T;T

MetaSVM

Benign

-0.93

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.8

.;D;.;.;.;.

REVEL

Benign

0.22

Sift

Benign

0.044

.;D;.;.;.;.

Sift4G

Uncertain

0.026

D;D;D;D;D;D

Polyphen

0.28

B;P;.;.;.;B

Vest4

0.52

MutPred

0.63

Loss of MoRF binding (P = 0.0564);Loss of MoRF binding (P = 0.0564);Loss of MoRF binding (P = 0.0564);Loss of MoRF binding (P = 0.0564);Loss of MoRF binding (P = 0.0564);Loss of MoRF binding (P = 0.0564);

MVP

0.54

MPC

0.64

ClinPred

0.34

GERP RS

0.52

Varity_R

0.11

gMVP

0.20

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