10-80132800-T-C

Position:

• chr10-80132800-T-C

Variant summary

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

The NM_001012973.3(PLAC9):​c.38T>C​(p.Leu13Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000446 in 1,346,214 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000045 (0 hom.)
• Consequence: PLAC9 NM_001012973.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.21

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLAC9	NM_001012973.3	c.38T>C	p.Leu13Pro	missense_variant	1/4	ENST00000372263.4
PLAC9	NM_001331125.2	c.38T>C	p.Leu13Pro	missense_variant	1/3
PLAC9	NR_138551.2	n.171+969T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLAC9	ENST00000372263.4	c.38T>C	p.Leu13Pro	missense_variant	1/4	1	NM_001012973.3	P1
PLAC9	ENST00000372267.6	c.38T>C	p.Leu13Pro	missense_variant	1/3	3
PLAC9	ENST00000372270.6	c.-63+969T>C		intron_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000446 AC: 6 AN: 1346214 Hom.: 0 Cov.: 30 AF XY: 0.00000753 AC XY: 5 AN XY: 663758

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000323

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000188

Gnomad4 OTH exome AF: 0.0000534

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000435 Hom.: 0

Bravo AF: 0.0000113

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

Oct 12, 2022

The c.38T>C (p.L13P) alteration is located in exon 1 (coding exon 1) of the PLAC9 gene. This alteration results from a T to C substitution at nucleotide position 38, causing the leucine (L) at amino acid position 13 to be replaced by a proline (P). 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	0.39
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.32
CADD	Pathogenic	28
DANN	Benign	0.97
DEOGEN2	Benign	0.12	T;T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.089
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.41	T;T
M_CAP	Uncertain	0.15	D
MetaRNN	Uncertain	0.67	D;D
MetaSVM	Benign	-0.45	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-4.9	D;D
REVEL	Uncertain	0.59
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.011	D;D
Polyphen		1.0	.;D
Vest4		0.82
MutPred		0.28		Loss of stability (P = 0.0219);Loss of stability (P = 0.0219);
MVP		0.12
MPC		0.29
ClinPred		0.93	D
GERP RS		2.8
Varity_R		0.79
gMVP		0.28

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: rs1045018131; hg19: chr10-81892556;