Genetic Variant PLAC1:p.Thr205Arg (chrX-134566069-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_021796.4(PLAC1):c.614C>G(p.Thr205Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000456 in 1,095,921 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000046 ( 0 hom. 1 hem. )

Consequence

PLAC1
NM_021796.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0310

Publications

0 publications found

Variant links:

Genes affected

PLAC1 (HGNC:9044): (placenta enriched 1) Involved in placenta development. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

PLAC1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06052363).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021796.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLAC1	NM_021796.4	MANE Select	c.614C>G	p.Thr205Arg	missense	Exon 3 of 3	NP_068568.1	Q9HBJ0
PLAC1	NM_001316887.2		c.614C>G	p.Thr205Arg	missense	Exon 4 of 4	NP_001303816.1	Q9HBJ0
PLAC1	NM_001316888.2		c.614C>G	p.Thr205Arg	missense	Exon 3 of 3	NP_001303817.1	Q9HBJ0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLAC1	ENST00000359237.9	TSL:1 MANE Select	c.614C>G	p.Thr205Arg	missense	Exon 3 of 3	ENSP00000352173.4	Q9HBJ0
PLAC1	ENST00000878501.1		c.614C>G	p.Thr205Arg	missense	Exon 4 of 4	ENSP00000548560.1
PLAC1	ENST00000917137.1		c.614C>G	p.Thr205Arg	missense	Exon 2 of 2	ENSP00000587196.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000109

AC:

AN:

183081

AF XY:

0.0000148

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000245

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000456

AC:

AN:

1095921

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

361333

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26366

American (AMR)

AF:

0.00

AC:

AN:

35203

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19359

East Asian (EAS)

AF:

0.00

AC:

AN:

30198

South Asian (SAS)

AF:

0.00

AC:

AN:

54064

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40483

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4130

European-Non Finnish (NFE)

AF:

0.00000595

AC:

AN:

840096

Other (OTH)

AF:

0.00

AC:

AN:

46022

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.76

CADD

Benign

5.4

(source)

DANN

Benign

0.61

DEOGEN2

Benign

0.034

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.24

M_CAP

Benign

0.0024

MetaRNN

Benign

0.061

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.031

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.28

REVEL

Benign

0.055

Sift

Benign

0.33

Sift4G

Benign

0.15

Polyphen

0.36

Vest4

0.25

MutPred

0.092

Gain of phosphorylation at S202 (P = 0.086)

MVP

0.14

MPC

0.14

ClinPred

0.062

GERP RS

-0.49

Varity_R

0.072

gMVP

0.49

Mutation Taster

=100/0

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over