chr8-98123347-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001145860.2(POP1):c.10G>A(p.Ala4Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00341 in 1,613,516 control chromosomes in the GnomAD database, including 80 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A4P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0019 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0036 ( 77 hom. )

Consequence

POP1
NM_001145860.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.58

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006253153).

BP6

Variant 8-98123347-G-A is Benign according to our data. Variant chr8-98123347-G-A is described in ClinVar as [Benign]. Clinvar id is 724459.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00192 (292/152214) while in subpopulation SAS AF = 0.0327 (157/4806). AF 95% confidence interval is 0.0285. There are 3 homozygotes in GnomAd4. There are 170 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POP1	NM_001145860.2 link	c.10G>A	p.Ala4Thr	missense_variant	Exon 2 of 16	ENST00000401707.7	NP_001139332.1
POP1	NM_001145861.2 link	c.10G>A	p.Ala4Thr	missense_variant	Exon 2 of 16		NP_001139333.1	Q99575
POP1	NM_015029.3 link	c.10G>A	p.Ala4Thr	missense_variant	Exon 2 of 16		NP_055844.2	Q99575Q96F88
POP1	XM_011516801.3 link	c.10G>A	p.Ala4Thr	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.10G>A	p.Ala4Thr	missense_variant	Exon 2 of 16	2	NM_001145860.2	ENSP00000385787.2	Q99575
POP1	ENST00000349693.3 link	c.10G>A	p.Ala4Thr	missense_variant	Exon 2 of 16	1		ENSP00000339529.3	Q99575
POP1	ENST00000522319.5 link	c.10G>A	p.Ala4Thr	missense_variant	Exon 2 of 5	4		ENSP00000428945.1	E5RK39

Frequencies

GnomAD3 genomes

AF:

0.00193

AC:

294

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00950

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0326

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00118

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.00556

AC:

1397

AN:

251424

AF XY:

0.00711

show subpopulations

Gnomad AFR exome

AF:

0.000861

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00992

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00152

Gnomad OTH exome

AF:

0.00359

GnomAD4 exome

AF:

0.00356

AC:

5208

AN:

1461302

Hom.:

Cov.:

AF XY:

0.00450

AC XY:

3272

AN XY:

727006

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

AC:

AN:

33464

Gnomad4 AMR exome

AF:

0.0000447

AC:

AN:

44706

Gnomad4 ASJ exome

AF:

0.00938

AC:

245

AN:

26110

Gnomad4 EAS exome

AF:

0.0000252

AC:

AN:

39664

Gnomad4 SAS exome

AF:

0.0343

AC:

2955

AN:

86252

Gnomad4 FIN exome

AF:

0.000206

AC:

AN:

53358

Gnomad4 NFE exome

AF:

0.00152

AC:

1689

AN:

1111628

Gnomad4 Remaining exome

AF:

0.00436

AC:

263

AN:

60356

Heterozygous variant carriers

274

548

821

1095

1369

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

100

200

300

400

500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00192

AC:

292

AN:

152214

Hom.:

Cov.:

AF XY:

0.00228

AC XY:

170

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.000482

AC:

0.000481626

AN:

0.000481626

Gnomad4 AMR

AF:

0.0000654

AC:

0.0000653937

AN:

0.0000653937

Gnomad4 ASJ

AF:

0.00950

AC:

0.00950461

AN:

0.00950461

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.0327

AC:

0.0326675

AN:

0.0326675

Gnomad4 FIN

AF:

0.0000944

AC:

0.0000943574

AN:

0.0000943574

Gnomad4 NFE

AF:

0.00116

AC:

0.00116159

AN:

0.00116159

Gnomad4 OTH

AF:

0.000474

AC:

0.000473934

AN:

0.000473934

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00176

Hom.:

Bravo

AF:

0.00114

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00209

AC:

ExAC

AF:

0.00587

AC:

713

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.00115

EpiControl

AF:

0.00142

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.78

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.031

T;T;T

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.82

T;.;T

MetaRNN

Benign

0.0063

T;T;T

MetaSVM

Benign

-0.39

MutationAssessor

Uncertain

2.7

.;M;M

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.6

N;N;N

REVEL

Benign

0.15

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.49, 0.49

MVP

0.75

MPC

0.72

ClinPred

0.053

GERP RS

4.9

Varity_R

0.41

gMVP

0.55

Mutation Taster

=100/0

polymorphism

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