rs770452677

Variant names:

• chr11-63490963-T-G
• rs770452677
• NM_001146729.2:c.72A>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001146729.2(PLAAT5):​c.72A>C​(p.Lys24Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 0.00037 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000064 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PLAAT5 NM_001146729.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.383
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.026563168).

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.72A>C	p.Lys24Asn	missense	Exon 1 of 6	NP_001140201.2	Q96KN8-3
	PLAAT5	NM_054108.4		c.72A>C	p.Lys24Asn	missense	Exon 1 of 6	NP_473449.2	Q96KN8-1
	PLAAT5	NM_001146728.2		c.72A>C	p.Lys24Asn	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.72A>C	p.Lys24Asn	missense	Exon 1 of 6	ENSP00000444809.1	Q96KN8-3
	PLAAT5	ENST00000301790.4	TSL:1	c.72A>C	p.Lys24Asn	missense	Exon 1 of 6	ENSP00000301790.4	Q96KN8-1
	PLAAT5	ENST00000539221.5	TSL:1	c.72A>C	p.Lys24Asn	missense	Exon 1 of 6	ENSP00000443873.1	Q96KN8-2

Frequencies

GnomAD3 genomes AF: 0.000373 AC: 56 AN: 150168 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000731

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000660

Gnomad ASJ AF: 0.00117

Gnomad EAS AF: 0.000198

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00333

Gnomad NFE AF: 0.000686

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000422 AC: 82 AN: 194306 AF XY: 0.000416

Gnomad AFR exome AF: 0.000552

Gnomad AMR exome AF: 0.000103

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000139

Gnomad FIN exome AF: 0.00284

Gnomad NFE exome AF: 0.000275

Gnomad OTH exome AF: 0.000202

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000636 AC: 91 AN: 1430402 Hom.: 0 Cov.: 33 AF XY: 0.0000761 AC XY: 54 AN XY: 709620

⚠️ 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: 32322

American (AMR) AF: 0.0000248 AC: 1 AN: 40320

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25278

East Asian (EAS) AF: 0.00 AC: 0 AN: 37584

South Asian (SAS) AF: 0.00 AC: 0 AN: 82884

European-Finnish (FIN) AF: 0.00157 AC: 78 AN: 49826

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5556

European-Non Finnish (NFE) AF: 0.00000911 AC: 10 AN: 1097520

Other (OTH) AF: 0.0000338 AC: 2 AN: 59112

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000373 AC: 56 AN: 150278 Hom.: 0 Cov.: 32 AF XY: 0.000450 AC XY: 33 AN XY: 73314

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

African (AFR) AF: 0.0000729 AC: 3 AN: 41126

American (AMR) AF: 0.0000659 AC: 1 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.00117 AC: 4 AN: 3426

East Asian (EAS) AF: 0.000198 AC: 1 AN: 5052

South Asian (SAS) AF: 0.00 AC: 0 AN: 4752

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10460

Middle Eastern (MID) AF: 0.00360 AC: 1 AN: 278

European-Non Finnish (NFE) AF: 0.000686 AC: 46 AN: 67036

Other (OTH) AF: 0.00 AC: 0 AN: 2080

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ExAC AF: 0.000282 AC: 34

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	0.29
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Benign	0.47
DEOGEN2	Benign	0.0041	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.027	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L
PhyloP100		-0.38
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.023
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.42	B
Vest4		0.12
MutPred		0.20		Loss of methylation at K24 (P = 0.0011)
MVP		0.25
MPC		0.20
ClinPred		0.031	T
GERP RS		-0.15
PromoterAI		0.13	Neutral
Varity_R		0.071
gMVP		0.19
Mutation Taster		=99/1	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: rs770452677; hg19: chr11-63258435;