chr11-63491031-C-T

Variant names:

• chr11-63491031-C-T
• rs368931250
• NM_001146729.2:c.4G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001146729.2(PLAAT5):​c.4G>A​(p.Gly2Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000152 in 1,445,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000098 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000054 (0 hom.)
• Consequence: PLAAT5 NM_001146729.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.72
• Publications: 0 publications found

Genes affected

PLAAT5 (HGNC:24978): (phospholipase A and acyltransferase 5) Enables N-acyltransferase activity; phospholipase A1 activity; and phospholipase A2 activity. Acts upstream of or within N-acylphosphatidylethanolamine metabolic process. Predicted to be located in cytosol. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000287412 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.33318824).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146729.2. 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
	PLAAT5	NM_001146729.2	MANE Select	c.4G>A	p.Gly2Ser	missense	Exon 1 of 6	NP_001140201.2	Q96KN8-3
	PLAAT5	NM_054108.4		c.4G>A	p.Gly2Ser	missense	Exon 1 of 6	NP_473449.2	Q96KN8-1
	PLAAT5	NM_001146728.2		c.4G>A	p.Gly2Ser	missense	Exon 1 of 6	NP_001140200.2	Q96KN8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAAT5	ENST00000540857.6	TSL:1 MANE Select	c.4G>A	p.Gly2Ser	missense	Exon 1 of 6	ENSP00000444809.1	Q96KN8-3
	PLAAT5	ENST00000301790.4	TSL:1	c.4G>A	p.Gly2Ser	missense	Exon 1 of 6	ENSP00000301790.4	Q96KN8-1
	PLAAT5	ENST00000539221.5	TSL:1	c.4G>A	p.Gly2Ser	missense	Exon 1 of 6	ENSP00000443873.1	Q96KN8-2

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.000478

GnomAD2 exomes AF: 0.00 AC: 0 AN: 54334 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000541 AC: 7 AN: 1293604 Hom.: 0 Cov.: 32 AF XY: 0.00000475 AC XY: 3 AN XY: 631398

African (AFR) AF: 0.000156 AC: 4 AN: 25652

American (AMR) AF: 0.00 AC: 0 AN: 20172

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18798

East Asian (EAS) AF: 0.00 AC: 0 AN: 30588

South Asian (SAS) AF: 0.00 AC: 0 AN: 64972

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43934

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4064

European-Non Finnish (NFE) AF: 0.00000194 AC: 2 AN: 1032406

Other (OTH) AF: 0.0000189 AC: 1 AN: 53018

GnomAD4 genome AF: 0.0000985 AC: 15 AN: 152308 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74470

African (AFR) AF: 0.000313 AC: 13 AN: 41576

American (AMR) AF: 0.0000653 AC: 1 AN: 15306

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000869

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	0.38
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0075	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.074
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.0	L
PhyloP100		2.7
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.16
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.35
MutPred		0.16		Gain of phosphorylation at G2 (P = 0.0123)
MVP		0.42
MPC		0.58
ClinPred		0.88	D
GERP RS		2.6
PromoterAI		-0.040	Neutral
Varity_R		0.16
gMVP		0.42
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs368931250; hg19: chr11-63258503; COSMIC: COSV57138438; COSMIC: COSV57138438;