rs201688333

Variant names:

• chr11-63598091-C-A
• rs201688333
• NM_001128203.2:c.88G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-63598091-C-A
• chr11-63598091-C-T

Variant summary

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

The NM_001128203.2(PLAAT3):​c.88G>T​(p.Asp30Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. D30N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PLAAT3 NM_001128203.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.658
• Publications: 1 publications found

Genes affected

PLAAT3 (HGNC:17825): (phospholipase A and acyltransferase 3) Enables N-acyltransferase activity; phospholipase A1 activity; and phospholipase A2 activity. Involved in N-acylphosphatidylethanolamine metabolic process. Predicted to be located in several cellular components, including lysosome; nuclear envelope; and peroxisome. Predicted to be active in cytoplasm. Biomarker of seminoma. [provided by Alliance of Genome Resources, Apr 2022]

PLAAT3 Gene-Disease associations (from GenCC):

• lipodystrophy, familial partial, type 9

  Inheritance: AR Classification: LIMITED Submitted by: G2P, Ambry Genetics

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=0.27560055).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLAAT3	NM_001128203.2	c.88G>T	p.Asp30Tyr	missense_variant	Exon 3 of 5	ENST00000415826.3	NP_001121675.1
PLAAT3	NM_007069.3	c.88G>T	p.Asp30Tyr	missense_variant	Exon 2 of 4		NP_009000.2
PLAAT3	XM_011544741.2	c.133G>T	p.Asp45Tyr	missense_variant	Exon 2 of 4		XP_011543043.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLAAT3	ENST00000415826.3	c.88G>T	p.Asp30Tyr	missense_variant	Exon 3 of 5	2	NM_001128203.2	ENSP00000389124.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461186 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726936

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111388

Other (OTH) AF: 0.00 AC: 0 AN: 60372

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152190 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74336

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000241 AC: 1 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2090

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.14	T;.;T
Eigen	Benign	-0.089
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.73	.;T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.28	T;T;T
MetaSVM	Benign	-1.0	T
PhyloP100		0.66
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-5.4	D;.;D
REVEL	Benign	0.16
Sift	Uncertain	0.0050	D;.;D
Sift4G	Uncertain	0.0050	D;.;D
Polyphen		0.25	B;.;B
Vest4		0.74
MutPred		0.51		Gain of phosphorylation at D30 (P = 0.045);.;Gain of phosphorylation at D30 (P = 0.045);
MVP		0.55
MPC		0.39
ClinPred		0.97	D
GERP RS		1.9
Varity_R		0.61
gMVP		0.64
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs201688333; hg19: chr11-63365563;