chr10-80142090-C-T

Position:

• chr10-80142090-C-T

Variant summary

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

The NM_001012973.3(PLAC9):​c.73C>T​(p.Pro25Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,455,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PLAC9 NM_001012973.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.794

Genes affected

PLAC9 (HGNC:19255): (placenta associated 9) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

PLAC9 (HGNC:):

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=0.14941296).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLAC9	NM_001012973.3	c.73C>T	p.Pro25Ser	missense_variant	2/4	ENST00000372263.4	NP_001012991.1
PLAC9	NM_001331125.2	c.73C>T	p.Pro25Ser	missense_variant	2/3		NP_001318054.1
PLAC9	NR_138551.2	n.180C>T		non_coding_transcript_exon_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLAC9	ENST00000372263.4	c.73C>T	p.Pro25Ser	missense_variant	2/4	1	NM_001012973.3	ENSP00000361337.3
PLAC9	ENST00000372267.6	c.73C>T	p.Pro25Ser	missense_variant	2/3	3		ENSP00000361341.2
PLAC9	ENST00000372270	c.-54C>T		5_prime_UTR_variant	2/4	2		ENSP00000361344.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1455780 Hom.: 0 Cov.: 30 AF XY: 0.00000277 AC XY: 2 AN XY: 723236

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: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2023

The c.73C>T (p.P25S) alteration is located in exon 2 (coding exon 2) of the PLAC9 gene. This alteration results from a C to T substitution at nucleotide position 73, causing the proline (P) at amino acid position 25 to be replaced by a serine (S). 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	Benign	0.098
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T;T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.47	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-7.8	D;D
REVEL	Benign	0.091
Sift	Pathogenic	0.0	D;D
Sift4G	Benign	0.14	T;T
Polyphen		0.29	.;B
Vest4		0.39
MutPred		0.16		Gain of phosphorylation at P25 (P = 0.0245);Gain of phosphorylation at P25 (P = 0.0245);
MVP		0.030
MPC		0.26
ClinPred		0.91	D
GERP RS		1.9
Varity_R		0.47
gMVP		0.23

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: chr10-81901846;