X-134566286-C-T

Variant names:

• chrX-134566286-C-T
• rs1448603217
• NM_021796.4:c.397G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021796.4(PLAC1):​c.397G>A​(p.Ala133Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000892 in 112,045 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A133P) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 23)
• Consequence: PLAC1 NM_021796.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.669

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]

ACMG classification

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=0.085757494).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLAC1	NM_021796.4	c.397G>A	p.Ala133Thr	missense_variant	Exon 3 of 3	ENST00000359237.9	NP_068568.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLAC1	ENST00000359237.9	c.397G>A	p.Ala133Thr	missense_variant	Exon 3 of 3	1	NM_021796.4	ENSP00000352173.4
PLAC1	ENST00000476971.5	n.729G>A		non_coding_transcript_exon_variant	Exon 3 of 3	5
PLAC1	ENST00000473897.1	n.*224G>A		downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.00000892 AC: 1 AN: 112045 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34203

Gnomad AFR AF: 0.00

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: 0.0000188

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000892 AC: 1 AN: 112045 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34203

Gnomad4 AFR AF: 0.00

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: 0.0000188

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	5.5
DANN	Uncertain	0.98
DEOGEN2	Benign	0.050	T
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.13
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.054	T
Polyphen		0.13	B
Vest4		0.046
MutPred		0.12		Gain of phosphorylation at A133 (P = 0.0145);
MVP		0.67
MPC		0.10
ClinPred		0.25	T
GERP RS		-0.42
Varity_R		0.064
gMVP		0.19

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

Other links and lift over

dbSNP: rs1448603217; hg19: chrX-133700316;