X-134566541-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 12/20 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: 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

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 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLAC1	NM_021796.4	c.142G>C	p.Val48Leu	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.142G>C	p.Val48Leu	missense_variant	Exon 3 of 3	1	NM_021796.4	ENSP00000352173.4
PLAC1	ENST00000473897.1	n.302G>C		non_coding_transcript_exon_variant	Exon 3 of 3	5
PLAC1	ENST00000476971.5	n.474G>C		non_coding_transcript_exon_variant	Exon 3 of 3	5

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

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: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 30, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.142G>C (p.V48L) alteration is located in exon 3 (coding exon 1) of the PLAC1 gene. This alteration results from a G to C substitution at nucleotide position 142, causing the valine (V) at amino acid position 48 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	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
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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-133700571;