Genetic Variant NM_001145860.2:c.1573C>T (chr8-98140867-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 3P and 1B. PM2PP5BP4

The NM_001145860.2(POP1):c.1573C>T(p.Pro525Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. P525P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

POP1
NM_001145860.2 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 1.35

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

anauxetic dysplasia 2
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
anauxetic dysplasia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

POP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 8-98140867-C-T is Pathogenic according to our data. Variant chr8-98140867-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 393588.Status of the report is no_assertion_criteria_provided, 0 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.08873084). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POP1	NM_001145860.2 link	c.1573C>T	p.Pro525Ser	missense_variant	Exon 11 of 16	ENST00000401707.7	NP_001139332.1
POP1	NM_001145861.2 link	c.1573C>T	p.Pro525Ser	missense_variant	Exon 11 of 16		NP_001139333.1	Q99575
POP1	NM_015029.3 link	c.1573C>T	p.Pro525Ser	missense_variant	Exon 11 of 16		NP_055844.2	Q99575Q96F88
POP1	XM_011516801.3 link	c.1573C>T	p.Pro525Ser	missense_variant	Exon 11 of 12		XP_011515103.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POP1	ENST00000401707.7 link	c.1573C>T	p.Pro525Ser	missense_variant	Exon 11 of 16	2	NM_001145860.2	ENSP00000385787.2		Q99575
POP1	ENST00000349693.3 link	c.1573C>T	p.Pro525Ser	missense_variant	Exon 11 of 16	1		ENSP00000339529.3		Q99575

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251356

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000256

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Anauxetic dysplasia 2

Pathogenic:1

Apr 10, 2017

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.18

T;T

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.73

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.64

.;T

M_CAP

Benign

0.0047

MetaRNN

Benign

0.089

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L

PhyloP100

1.4

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-3.2

D;D

REVEL

Benign

0.13

Sift

Benign

0.15

T;T

Sift4G

Benign

0.15

T;T

Polyphen

0.012

B;B

Vest4

0.092

MVP

0.33

MPC

0.20

ClinPred

0.093

GERP RS

-0.58

Varity_R

0.17

gMVP

0.34

Mutation Taster

=34/66

disease causing (ClinVar)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over