Variant 8-98123411-G-C 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_001145860.2(POP1):c.74G>C(p.Gly25Ala) 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 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

POP1
NM_001145860.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.25

Variant links:

Genes affected

POP1 (HGNC:30129): (POP1 homolog, ribonuclease P/MRP subunit) This gene encodes the protein subunit of two different small nucleolar ribonucleoprotein complexes: the endoribonuclease for mitochondrial RNA processing complex and the ribonuclease P complex. The encoded protein is a ribonuclease that localizes to the nucleus and functions in pre-RNA processing. This protein is also an autoantigen in patients suffering from connective tissue diseases. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2009]

POP1 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=0.19933072).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POP1	NM_001145860.2 link	c.74G>C	p.Gly25Ala	missense_variant	Exon 2 of 16	ENST00000401707.7	NP_001139332.1
POP1	NM_001145861.2 link	c.74G>C	p.Gly25Ala	missense_variant	Exon 2 of 16		NP_001139333.1	Q99575
POP1	NM_015029.3 link	c.74G>C	p.Gly25Ala	missense_variant	Exon 2 of 16		NP_055844.2	Q99575Q96F88
POP1	XM_011516801.3 link	c.74G>C	p.Gly25Ala	missense_variant	Exon 2 of 12		XP_011515103.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
POP1	ENST00000401707.7 link	c.74G>C	p.Gly25Ala	missense_variant	Exon 2 of 16	2	NM_001145860.2	ENSP00000385787.2	Q99575
POP1	ENST00000349693.3 link	c.74G>C	p.Gly25Ala	missense_variant	Exon 2 of 16	1		ENSP00000339529.3	Q99575
POP1	ENST00000522319.5 link	c.74G>C	p.Gly25Ala	missense_variant	Exon 2 of 5	4		ENSP00000428945.1	E5RK39

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251484

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135920

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461808

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727208

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.027

T;T;T

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.77

T;.;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.20

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.6

.;M;M

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.029

Sift

Benign

0.15

T;T;T

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.89

.;P;P

Vest4

0.36, 0.34

MutPred

0.27

Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);

MVP

0.68

MPC

0.37

ClinPred

0.54

GERP RS

4.9

Varity_R

0.076

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over