dbSNP rs926275861: POP1:p.Leu22Met (chr8-98123401-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001145860.2(POP1):c.64C>A(p.Leu22Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

POP1
NM_001145860.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00400

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:

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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=0.11851537).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POP1	NM_001145860.2 link	c.64C>A	p.Leu22Met	missense_variant	Exon 2 of 16	ENST00000401707.7	NP_001139332.1
POP1	NM_001145861.2 link	c.64C>A	p.Leu22Met	missense_variant	Exon 2 of 16		NP_001139333.1	Q99575
POP1	NM_015029.3 link	c.64C>A	p.Leu22Met	missense_variant	Exon 2 of 16		NP_055844.2	Q99575Q96F88
POP1	XM_011516801.3 link	c.64C>A	p.Leu22Met	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.64C>A	p.Leu22Met	missense_variant	Exon 2 of 16	2	NM_001145860.2	ENSP00000385787.2	Q99575
POP1	ENST00000349693.3 link	c.64C>A	p.Leu22Met	missense_variant	Exon 2 of 16	1		ENSP00000339529.3	Q99575
POP1	ENST00000522319.5 link	c.64C>A	p.Leu22Met	missense_variant	Exon 2 of 5	4		ENSP00000428945.1	E5RK39

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251490

Hom.:

AF XY:

0.00

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:

0.00000137

AC:

AN:

1461816

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727226

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.078

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.021

T;T;T

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.69

T;.;T

M_CAP

Benign

0.032

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.7

.;M;M

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.71

N;N;N

REVEL

Benign

0.095

Sift

Uncertain

0.016

D;D;D

Sift4G

Uncertain

0.015

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.44, 0.44

MutPred

0.33

Gain of catalytic residue at L22 (P = 0.0117);Gain of catalytic residue at L22 (P = 0.0117);Gain of catalytic residue at L22 (P = 0.0117);

MVP

0.41

MPC

0.73

ClinPred

0.75

GERP RS

0.70

Varity_R

0.070

gMVP

0.15

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over