X-134566541-C-G

Variant names:

• chrX-134566541-C-G
• rs1185530130
• NM_021796.4:c.142G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_021796.4(PLAC1):​c.142G>C​(p.Val48Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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: 9.1e-7 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: PLAC1 NM_021796.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.98
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35977983).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAC1	NM_021796.4	MANE Select	c.142G>C	p.Val48Leu	missense	Exon 3 of 3	NP_068568.1	Q9HBJ0
	PLAC1	NM_001316887.2		c.142G>C	p.Val48Leu	missense	Exon 4 of 4	NP_001303816.1	Q9HBJ0
	PLAC1	NM_001316888.2		c.142G>C	p.Val48Leu	missense	Exon 3 of 3	NP_001303817.1	Q9HBJ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAC1	ENST00000359237.9	TSL:1 MANE Select	c.142G>C	p.Val48Leu	missense	Exon 3 of 3	ENSP00000352173.4	Q9HBJ0
	PLAC1	ENST00000878501.1		c.142G>C	p.Val48Leu	missense	Exon 4 of 4	ENSP00000548560.1
	PLAC1	ENST00000917137.1		c.142G>C	p.Val48Leu	missense	Exon 2 of 2	ENSP00000587196.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.11e-7 AC: 1 AN: 1098107 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 1 AN XY: 363463

African (AFR) AF: 0.00 AC: 0 AN: 26400

American (AMR) AF: 0.00 AC: 0 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40520

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4126

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 842024

Other (OTH) AF: 0.00 AC: 0 AN: 46096

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.030	T
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.61	T
M_CAP	Pathogenic	0.63	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	1.7	L
PhyloP100		3.0
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.25
Sift	Benign	0.29	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.35
MutPred		0.26		Loss of catalytic residue at V48 (P = 0.2903)
MVP		0.76
MPC		0.47
ClinPred		0.40	T
GERP RS		4.3
Varity_R		0.11
gMVP		0.60
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs1185530130; hg19: chrX-133700571;