Variant 10-80144226-G-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.166G>T(p.Val56Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

PLAC9
NM_001012973.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.52

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:

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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=0.16299847).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLAC9	NM_001012973.3 linkuse as main transcript	c.166G>T	p.Val56Leu	missense_variant	3/4	ENST00000372263.4	NP_001012991.1	Q5JTB6
PLAC9	NM_001331125.2 linkuse as main transcript	c.163-674G>T		intron_variant			NP_001318054.1	Q5JTB6Q5JTB5
PLAC9	NR_138551.2 linkuse as main transcript	n.273G>T		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.166G>T	p.Val56Leu	missense_variant	3/4	1	NM_001012973.3	ENSP00000361337.3	Q5JTB6
PLAC9	ENST00000372270.6 linkuse as main transcript	c.40G>T	p.Val14Leu	missense_variant	3/4	2		ENSP00000361344.1	Q5JTB4
PLAC9	ENST00000372267.6 linkuse as main transcript	c.163-674G>T		intron_variant		3		ENSP00000361341.2	Q5JTB5
PLAC9	ENST00000465660.1 linkuse as main transcript	n.179G>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251446

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135902

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461824

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727214

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000611

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000247

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

Jan 26, 2023

The c.166G>T (p.V56L) alteration is located in exon 3 (coding exon 3) of the PLAC9 gene. This alteration results from a G to T substitution at nucleotide position 166, causing the valine (V) at amino acid position 56 to be replaced by a leucine (L). 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

-0.14

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.16

.;T

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.64

T;T

M_CAP

Benign

0.0093

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-2.3

N;N

REVEL

Benign

0.13

Sift

Uncertain

0.016

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.11

.;B

Vest4

0.33

MutPred

0.13

.;Loss of methylation at K58 (P = 0.0778);

MVP

0.055

MPC

0.039

ClinPred

0.056

GERP RS

1.4

Varity_R

0.099

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