dbSNP rs1197954406: PLSCR4:p.Ala289Ser (chr3-146195204-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_020353.3(PLSCR4):c.865G>T(p.Ala289Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 1,460,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. 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. A289T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000089 ( 0 hom. )

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36044675).

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>T	p.Ala289Ser	missense	Exon 8 of 9	NP_065086.2	Q9NRQ2-1
PLSCR4	NM_001128304.2		c.865G>T	p.Ala289Ser	missense	Exon 10 of 11	NP_001121776.1	Q9NRQ2-1
PLSCR4	NM_001128305.2		c.865G>T	p.Ala289Ser	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>T	p.Ala289Ser	missense	Exon 8 of 9	ENSP00000347038.2	Q9NRQ2-1
PLSCR4	ENST00000446574.6	TSL:2	c.865G>T	p.Ala289Ser	missense	Exon 8 of 9	ENSP00000399315.2	Q9NRQ2-1
PLSCR4	ENST00000493382.5	TSL:2	c.865G>T	p.Ala289Ser	missense	Exon 10 of 11	ENSP00000419040.1	Q9NRQ2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000890

AC:

AN:

1460760

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726764

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33450

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39680

South Asian (SAS)

AF:

0.00

AC:

AN:

86216

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000117

AC:

AN:

1111034

Other (OTH)

AF:

0.00

AC:

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

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

0.15

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.036

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.67

M_CAP

Benign

0.025

MetaRNN

Benign

0.36

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.1

PhyloP100

0.13

PrimateAI

Benign

0.34

PROVEAN

Benign

-2.2

REVEL

Benign

0.12

Sift

Benign

0.078

Sift4G

Benign

0.086

Polyphen

0.96

Vest4

0.19

MutPred

0.80

Loss of catalytic residue at A289 (P = 0.0085)

MVP

0.28

MPC

0.41

ClinPred

0.62

GERP RS

3.9

Varity_R

0.15

gMVP

0.19

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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