Variant chr10-80144328-C-T 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.268C>T(p.Pro90Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Consequence

PLAC9
NM_001012973.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.992

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:

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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=0.2628489).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PLAC9	NM_001012973.3 linkuse as main transcript	c.268C>T	p.Pro90Ser	missense_variant	3/4	ENST00000372263.4
PLAC9	NM_001331125.2 linkuse as main transcript	c.163-572C>T		intron_variant
PLAC9	NR_138551.2 linkuse as main transcript	n.375C>T		non_coding_transcript_exon_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PLAC9	ENST00000372263.4 linkuse as main transcript	c.268C>T	p.Pro90Ser	missense_variant	3/4	1	NM_001012973.3	P1
PLAC9	ENST00000372270.6 linkuse as main transcript	c.142C>T	p.Pro48Ser	missense_variant	3/4	2
PLAC9	ENST00000372267.6 linkuse as main transcript	c.163-572C>T		intron_variant		3
PLAC9	ENST00000465660.1 linkuse as main transcript	n.281C>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152014

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74232

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

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

Nov 08, 2022

The c.268C>T (p.P90S) alteration is located in exon 3 (coding exon 3) of the PLAC9 gene. This alteration results from a C to T substitution at nucleotide position 268, causing the proline (P) at amino acid position 90 to be replaced by a serine (S). 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

0.11

BayesDel_addAF

Benign

-0.031

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.0086

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.77

T;T

M_CAP

Benign

0.026

MetaRNN

Benign

0.26

T;T

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-5.3

D;D

REVEL

Benign

0.052

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.17

T;D

Polyphen

1.0

.;D

Vest4

0.37

MutPred

0.27

.;Loss of catalytic residue at P90 (P = 0.0247);

MVP

0.099

MPC

0.26

ClinPred

0.99

GERP RS

2.8

Varity_R

0.25

gMVP

0.12

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