rs375158196

Variant names:

• chr11-63468419-A-G
• rs375158196
• NM_001146729.2:c.392T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001146729.2(PLAAT5):​c.392T>C​(p.Ile131Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00029 in 1,614,058 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00030 (1 hom.)
• Consequence: PLAAT5 NM_001146729.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.741
• Publications: 4 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08790523).

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.392T>C	p.Ile131Thr	missense	Exon 4 of 6	NP_001140201.2	Q96KN8-3
	PLAAT5	NM_054108.4		c.422T>C	p.Ile141Thr	missense	Exon 4 of 6	NP_473449.2	Q96KN8-1
	PLAAT5	NM_001146728.2		c.422T>C	p.Ile141Thr	missense	Exon 4 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.392T>C	p.Ile131Thr	missense	Exon 4 of 6	ENSP00000444809.1	Q96KN8-3
	PLAAT5	ENST00000301790.4	TSL:1	c.422T>C	p.Ile141Thr	missense	Exon 4 of 6	ENSP00000301790.4	Q96KN8-1
	PLAAT5	ENST00000539221.5	TSL:1	c.422T>C	p.Ile141Thr	missense	Exon 4 of 6	ENSP00000443873.1	Q96KN8-2

Frequencies

GnomAD3 genomes AF: 0.000184 AC: 28 AN: 152220 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

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: 0.000265

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.0000995 AC: 25 AN: 251380 AF XY: 0.000110

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: 0.000211

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000301 AC: 440 AN: 1461838 Hom.: 1 Cov.: 30 AF XY: 0.000285 AC XY: 207 AN XY: 727220

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

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

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000384 AC: 427 AN: 1111982

Other (OTH) AF: 0.000149 AC: 9 AN: 60394

GnomAD4 genome AF: 0.000184 AC: 28 AN: 152220 Hom.: 0 Cov.: 31 AF XY: 0.000175 AC XY: 13 AN XY: 74372

African (AFR) AF: 0.0000483 AC: 2 AN: 41450

American (AMR) AF: 0.000393 AC: 6 AN: 15284

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: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68042

Other (OTH) AF: 0.000956 AC: 2 AN: 2092

Alfa AF: 0.000213 Hom.: 0

Bravo AF: 0.000219

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000115 AC: 14

EpiCase AF: 0.000273

EpiControl AF: 0.000237

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	Benign	0.27
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.0040	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.082	N
LIST_S2	Benign	0.087	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.51	N
PhyloP100		0.74
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.16
Sift	Benign	0.46	T
Sift4G	Benign	0.44	T
Polyphen		0.21	B
Vest4		0.20
MVP		0.29
MPC		0.53
ClinPred		0.27	T
GERP RS		4.4
Varity_R		0.090
gMVP		0.68
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs375158196; hg19: chr11-63235891; COSMIC: COSV57137998; COSMIC: COSV57137998;