Genetic Variant PLSCR4:p.Ala289Thr (chr3-146195204-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020353.3(PLSCR4):c.865G>A(p.Ala289Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,198 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A289S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Consequence

PLSCR4
NM_020353.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.126

Publications

0 publications found

Variant links:

Genes affected

PLSCR4 (HGNC:16497): (phospholipid scramblase 4) Enables CD4 receptor binding activity and enzyme binding activity. Predicted to be involved in plasma membrane phospholipid scrambling. Predicted to act upstream of or within cellular response to lipopolysaccharide. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

PLSCR4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020353.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLSCR4	NM_020353.3	MANE Select	c.865G>A	p.Ala289Thr	missense	Exon 8 of 9	NP_065086.2	Q9NRQ2-1
PLSCR4	NM_001128304.2		c.865G>A	p.Ala289Thr	missense	Exon 10 of 11	NP_001121776.1	Q9NRQ2-1
PLSCR4	NM_001128305.2		c.865G>A	p.Ala289Thr	missense	Exon 8 of 9	NP_001121777.1	Q9NRQ2-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLSCR4	ENST00000354952.7	TSL:1 MANE Select	c.865G>A	p.Ala289Thr	missense	Exon 8 of 9	ENSP00000347038.2	Q9NRQ2-1
PLSCR4	ENST00000446574.6	TSL:2	c.865G>A	p.Ala289Thr	missense	Exon 8 of 9	ENSP00000399315.2	Q9NRQ2-1
PLSCR4	ENST00000493382.5	TSL:2	c.865G>A	p.Ala289Thr	missense	Exon 10 of 11	ENSP00000419040.1	Q9NRQ2-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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

Cov.:

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41452

American (AMR)

AF:

0.00

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.090

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.69

M_CAP

Benign

0.021

MetaRNN

Uncertain

0.45

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.1

PhyloP100

0.13

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.13

Sift

Benign

0.14

Sift4G

Benign

0.23

Polyphen

0.92

Vest4

0.18

MutPred

0.84

Gain of sheet (P = 0.0827)

MVP

0.26

MPC

0.42

ClinPred

0.94

GERP RS

3.9

Varity_R

0.11

gMVP

0.25

Mutation Taster

=91/9

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over