Variant 10-80132808-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_001012973.3(PLAC9):c.46G>C(p.Ala16Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000334 in 1,497,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000030 ( 0 hom. )

Consequence

PLAC9
NM_001012973.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.16

Variant links:

Genes affected

PLAC9 (HGNC:19255): (placenta associated 9) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

PLAC9 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=0.20778996).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PLAC9	NM_001012973.3 linkuse as main transcript	c.46G>C	p.Ala16Pro	missense_variant	1/4	ENST00000372263.4
PLAC9	NM_001331125.2 linkuse as main transcript	c.46G>C	p.Ala16Pro	missense_variant	1/3
PLAC9	NR_138551.2 linkuse as main transcript	n.171+977G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PLAC9	ENST00000372263.4 linkuse as main transcript	c.46G>C	p.Ala16Pro	missense_variant	1/4	1	NM_001012973.3	P1
PLAC9	ENST00000372267.6 linkuse as main transcript	c.46G>C	p.Ala16Pro	missense_variant	1/3	3
PLAC9	ENST00000372270.6 linkuse as main transcript	c.-63+977G>C		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152228

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000108

AC:

AN:

92562

Hom.:

AF XY:

0.0000192

AC XY:

AN XY:

52002

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:

0.0000545

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000297

AC:

AN:

1344952

Hom.:

Cov.:

AF XY:

0.00000452

AC XY:

AN XY:

663176

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:

0.0000133

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.41e-7

Gnomad4 OTH exome

AF:

0.0000356

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74374

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000596

AC:

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 17, 2024

The c.46G>C (p.A16P) alteration is located in exon 1 (coding exon 1) of the PLAC9 gene. This alteration results from a G to C substitution at nucleotide position 46, causing the alanine (A) at amino acid position 16 to be replaced by a proline (P). 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

0.26

BayesDel_addAF

Benign

-0.027

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

T;T

Eigen

Uncertain

0.26

Eigen_PC

Benign

0.14

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.54

T;T

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.21

T;T

MetaSVM

Benign

-0.91

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-3.4

D;N

REVEL

Benign

0.23

Sift

Pathogenic

0.0

D;T

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

.;D

Vest4

0.32

MutPred

0.097

Loss of methylation at R15 (P = 0.072);Loss of methylation at R15 (P = 0.072);

MVP

0.17

MPC

0.27

ClinPred

0.99

GERP RS

2.8

Varity_R

0.50

gMVP

0.091

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