Variant chr19-45406700-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012099.3(POLR1G):c.4G>A(p.Glu2Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000455 in 1,539,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

POLR1G
NM_012099.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.64

Variant links:

Genes affected

POLR1G (HGNC:24219): (RNA polymerase I subunit G) Enables RNA binding activity. Predicted to be involved in transmembrane receptor protein tyrosine kinase signaling pathway. Predicted to act upstream of or within rRNA transcription. Located in cytosol; mitochondrion; and nuclear lumen. [provided by Alliance of Genome Resources, Apr 2022]

POLR1G links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16745862).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR1G	NM_012099.3 linkuse as main transcript	c.4G>A	p.Glu2Lys	missense_variant	1/3	ENST00000309424.8	NP_036231.1
POLR1G	NM_001297590.3 linkuse as main transcript	c.4G>A	p.Glu2Lys	missense_variant	1/3		NP_001284519.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLR1G	ENST00000309424.8 linkuse as main transcript	c.4G>A	p.Glu2Lys	missense_variant	1/3	1	NM_012099.3	ENSP00000310966	P4	O15446-1
POLR1G	ENST00000589804.1 linkuse as main transcript	c.4G>A	p.Glu2Lys	missense_variant	1/3	1		ENSP00000465099	A2	O15446-2
POLR1G	ENST00000590794.1 linkuse as main transcript	c.4G>A	p.Glu2Lys	missense_variant	1/2	5		ENSP00000466503
POLR1G	ENST00000592852.1 linkuse as main transcript	c.-906G>A		5_prime_UTR_variant	1/2	2		ENSP00000467771

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000360

AC:

AN:

1387380

Hom.:

Cov.:

AF XY:

0.00000438

AC XY:

AN XY:

684632

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000465

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000151

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

Jun 03, 2024

The c.4G>A (p.E2K) alteration is located in exon 1 (coding exon 1) of the CD3EAP gene. This alteration results from a G to A substitution at nucleotide position 4, causing the glutamic acid (E) at amino acid position 2 to be replaced by a lysine (K). 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

0.22

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

T;.

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.045

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.59

T;T

M_CAP

Benign

0.0068

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.72

N;.

REVEL

Benign

0.086

Sift

Benign

0.11

T;.

Sift4G

Benign

0.32

T;T

Polyphen

0.42

B;P

Vest4

0.14

MutPred

0.23

Gain of ubiquitination at E2 (P = 0.006);Gain of ubiquitination at E2 (P = 0.006);

MVP

0.34

MPC

0.27

ClinPred

0.78

GERP RS

4.0

Varity_R

0.19

gMVP

0.56

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