Genetic Variant PLAC1:p.Thr105Thr (chrX-134566368-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_021796.4(PLAC1):c.315G>A(p.Thr105Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,209,772 control chromosomes in the GnomAD database, including 13 homozygotes. There are 354 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0053 ( 8 hom., 164 hem., cov: 23)

Exomes 𝑓: 0.00067 ( 5 hom. 190 hem. )

Consequence

PLAC1
NM_021796.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.43

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant X-134566368-C-T is Benign according to our data. Variant chrX-134566368-C-T is described in ClinVar as [Benign]. Clinvar id is 783914.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00528 (591/111893) while in subpopulation AFR AF= 0.017 (523/30779). AF 95% confidence interval is 0.0158. There are 8 homozygotes in gnomad4. There are 164 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLAC1	NM_021796.4 link	c.315G>A	p.Thr105Thr	synonymous_variant	Exon 3 of 3	ENST00000359237.9	NP_068568.1	Q9HBJ0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PLAC1	ENST00000359237.9 link	c.315G>A	p.Thr105Thr	synonymous_variant	Exon 3 of 3	1	NM_021796.4	ENSP00000352173.4	Q9HBJ0
PLAC1	ENST00000476971.5 link	n.647G>A		non_coding_transcript_exon_variant	Exon 3 of 3	5
PLAC1	ENST00000473897.1 link	n.*142G>A		downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00526

AC:

588

AN:

111838

Hom.:

Cov.:

AF XY:

0.00473

AC XY:

161

AN XY:

34008

show subpopulations

Gnomad AFR

AF:

0.0169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00504

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000374

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00417

Gnomad NFE

AF:

0.000113

Gnomad OTH

AF:

0.00531

GnomAD3 exomes

AF:

0.00131

AC:

240

AN:

183381

Hom.:

AF XY:

0.000825

AC XY:

AN XY:

67855

show subpopulations

Gnomad AFR exome

AF:

0.0143

Gnomad AMR exome

AF:

0.00106

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000210

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000171

Gnomad OTH exome

AF:

0.00110

GnomAD4 exome

AF:

0.000667

AC:

732

AN:

1097879

Hom.:

Cov.:

AF XY:

0.000523

AC XY:

190

AN XY:

363237

show subpopulations

Gnomad4 AFR exome

AF:

0.0184

Gnomad4 AMR exome

AF:

0.00131

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000166

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000114

Gnomad4 OTH exome

AF:

0.00169

GnomAD4 genome

AF:

0.00528

AC:

591

AN:

111893

Hom.:

Cov.:

AF XY:

0.00481

AC XY:

164

AN XY:

34071

show subpopulations

Gnomad4 AFR

AF:

0.0170

Gnomad4 AMR

AF:

0.00504

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000375

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000113

Gnomad4 OTH

AF:

0.00524

Alfa

AF:

0.00253

Hom.:

Bravo

AF:

0.00645

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 21, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.039

DANN

Benign

0.32

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