Variant 10-80144304-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_001012973.3(PLAC9):c.244C>A(p.Pro82Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000687 in 1,611,810 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00072 ( 2 hom. )

Consequence

PLAC9
NM_001012973.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.05

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:

PLAC9 (HGNC:):

PLAC9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.839

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLAC9	NM_001012973.3 linkuse as main transcript	c.244C>A	p.Pro82Thr	missense_variant	3/4	ENST00000372263.4	NP_001012991.1	Q5JTB6
PLAC9	NM_001331125.2 linkuse as main transcript	c.163-596C>A		intron_variant			NP_001318054.1	Q5JTB6Q5JTB5
PLAC9	NR_138551.2 linkuse as main transcript	n.351C>A		non_coding_transcript_exon_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PLAC9	ENST00000372263.4 linkuse as main transcript	c.244C>A	p.Pro82Thr	missense_variant	3/4	1	NM_001012973.3	ENSP00000361337.3	Q5JTB6
PLAC9	ENST00000372270.6 linkuse as main transcript	c.118C>A	p.Pro40Thr	missense_variant	3/4	2		ENSP00000361344.1	Q5JTB4
PLAC9	ENST00000372267.6 linkuse as main transcript	c.163-596C>A		intron_variant		3		ENSP00000361341.2	Q5JTB5
PLAC9	ENST00000465660.1 linkuse as main transcript	n.257C>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.000381

AC:

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000779

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.000321

AC:

AN:

248850

Hom.:

AF XY:

0.000289

AC XY:

AN XY:

134768

show subpopulations

Gnomad AFR exome

AF:

0.0000619

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000499

Gnomad NFE exome

AF:

0.000628

Gnomad OTH exome

AF:

0.000820

GnomAD4 exome

AF:

0.000719

AC:

1049

AN:

1459740

Hom.:

Cov.:

AF XY:

0.000716

AC XY:

520

AN XY:

726284

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000117

Gnomad4 NFE exome

AF:

0.000874

Gnomad4 OTH exome

AF:

0.00111

GnomAD4 genome

AF:

0.000381

AC:

AN:

152070

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000779

Gnomad4 OTH

AF:

0.000480

Alfa

AF:

0.000410

Hom.:

Bravo

AF:

0.000389

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000305

AC:

EpiCase

AF:

0.000654

EpiControl

AF:

0.000415

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

Oct 06, 2024

The c.244C>A (p.P82T) alteration is located in exon 3 (coding exon 3) of the PLAC9 gene. This alteration results from a C to A substitution at nucleotide position 244, causing the proline (P) at amino acid position 82 to be replaced by a threonine (T). 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

0.23

BayesDel_addAF

Benign

-0.074

BayesDel_noAF

Uncertain

0.040

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

.;T

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.69

T;T

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.84

D;D

MetaSVM

Benign

-0.64

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-8.0

D;D

REVEL

Pathogenic

0.69

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

.;D

Vest4

0.70

MVP

0.13

MPC

0.28

ClinPred

0.82

GERP RS

3.8

Varity_R

0.67

gMVP

0.27

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